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1.
Organ Transplantation ; (6): 277-2022.
Article in Chinese | WPRIM | ID: wpr-920861

ABSTRACT

Mitochondria is one of the important organelles, which is composed of outer mitochondrial membrane and inner mitochondrial membrane. Mitochondrial structure and function are regulated by mitochondrial dynamics. Mitochondrial fusion- and fission-related proteins may participate in the process of mitochondrial fusion and fission, mediate mitochondrial dynamics, thereby regulating cell structure, function and energy metabolism. Mitofusin (MFN) 2, a protein located on the outer mitochondrial membrane of mammalian, has guanosine triphosphatase activity, which may mediate mitochondrial fusion, participate in mitophagy, formation of mitochondria-associated endoplasmic reticulum membrane and apoptosis, and significantly affect the incidence and development of ischemia-reperfusion injury (IRI). In this article, the structure, regulation, function of MFN2 and its role in IRI were reviewed, and the relationship between MFN2 and IRI and underlying mechanism were investigated, aiming to provide novel targets and ideas for the prevention and treatment of IRI.

2.
Article in Chinese | WPRIM | ID: wpr-907047

ABSTRACT

@#Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck. In recent years, the incidence rate has been increasing. Mitochondria are dynamic organelles involved in various cell behaviors in eukaryotic cells. Mitochondrial dysfunction is closely related to tumor development. As a switch that determines cancer cell death, targeting mitochondria has become the focus of OSCC treatment. This article reviews the relationship between mitochondria and tumorigenesis and development, OSCC treatment, and cisplatin resistant OSCC. Current studies have found that mitochondrial dysfunction promotes cell carcinogenesis, and the mitochondrial morphology and function of cancer cells are significantly changed. The increase of mitochondrial fission improves the invasiveness of cancer cells, and mitophagy dysfunction can induce cancer cell apoptosis. The emergence of drugs and the development of nanotechnology in targeted drug delivery systems have opened up new methods for targeting mitochondria to treat OSCC, reducing the side effects of systemic medication. The cisplatin resistance of OSCC is generated through the mitochondrial pathway, and the mitochondrial function and mutation mechanism of mitochondrial DNA are clarified in order to provide new ideas for targeting mitochondria to treat cisplatin resistant OSCC.

3.
China Pharmacy ; (12): 13-18, 2022.
Article in Chinese | WPRIM | ID: wpr-907006

ABSTRACT

OBJECTIVE To investigate the e ffects of methyl ferulate (MF) on the mitochondrial function of H 9c2 cardiomyocytes after hypoxia-induced injury. METHODS H9c2 cardiomyocytes were divided into normal group (no administration,no modeling ),hypoxia model group (modeling alone ),MF high-dose ,medium-dose and low-dose groups (40, 20,10 μmol/L)and positive control drug group (cyclosporin A ,1 μmol/L). After drug pretreatment and inducing hypoxia-induced injury,the levels of lactate dehydrogenase (LDH),malondialdehyde(MDA),creatine kinase (CK)and adenosine triphosphate (ATP)were tested. The intracellular reactive oxygen species (ROS),mitochondrial membrane potential (MMP),the opening of mitochondrial membrane permeability transition pore (mPTP) were detected with flow cytometry. RESULTS Compared with hypoxia model group ,the levels of LDH ,MDA,CK and ROS fluorescence intensity were decreased significantly in MF high-dose,medium-dose and low-dose groups ,while the level of ATP was increased significantly (P<0.01 or P<0.05). The red/ green fluorescence intensity ratio of MMP and the green fluorescence intensity of mPTP were increased significantly (P<0.01 or P<0.05). CONCLUSIONS MF can reverse the levels of biochemical indexes in H 9c2 cardiomyocyte after hypoxia-induced injury,keep MMP stable ,reduce the opening of mPTP ,and has an obvious protective effect on the mitochondrial function of H9c2 cardiomyocytes injured by hypoxia ,and this protective effect is dose-dependent.

4.
Article in English | WPRIM | ID: wpr-906679

ABSTRACT

@#BACKGROUND: Individuals who survive a cardiac arrest often sustain cognitive impairments due to ischemia-reperfusion injury. Mesenchymal stem cell (MSC) transplantation is used to reduce tissue damage, but exosomes are more stable and highly conserved than MSCs. This study was conducted to investigate the therapeutic effects of MSC-derived exosomes (MSC-Exo) on cerebral ischemia-reperfusion injury in an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R), and to explore the underlying mechanisms. METHODS: Primary hippocampal neurons obtained from 18-day Sprague-Dawley rat embryos were subjected to OGD/R treatment, with or without MSC-Exo treatment. Exosomal integration, cell viability, mitochondrial membrane potential, and generation of reactive oxygen species (ROS) were examined. Terminal deoxynucleotidyl transferase-mediated 2’-deoxyuridine 5’-triphosphate nick-end labeling (TUNEL) staining was performed to detect neuronal apoptosis. Moreover, mitochondrial function-associated gene expression, Nrf2 translocation, and expression of downstream antioxidant proteins were determined. RESULTS: MSC-Exo attenuated OGD/R-induced neuronal apoptosis and decreased ROS generation (P<0.05). The exosomes reduced OGD/R-induced Nrf2 translocation into the nucleus (2.14±0.65 vs. 5.48±1.09, P<0.01) and increased the intracellular expression of antioxidative proteins, including superoxide dismutase and glutathione peroxidase (17.18±0.97 vs. 14.40±0.62, and 20.65±2.23 vs. 16.44±2.05, respectively; P<0.05 for both). OGD/R significantly impaired the mitochondrial membrane potential and modulated the expression of mitochondrial function-associated genes, such as PINK, DJ1, LRRK2, Mfn-1, Mfn-2, and OPA1. The abovementioned changes were partially reversed by exosomal treatment of the hippocampal neurons. CONCLUSIONS: MSC-Exo treatment can alleviate OGD/R-induced oxidative stress and dysregulation of mitochondrial function-associated genes in hippocampal neurons. Therefore, MSC-Exo might be a potential therapeutic strategy to prevent OGD/R-induced neuronal injury.

5.
Acta Pharmaceutica Sinica ; (12): 681-694, 2022.
Article in Chinese | WPRIM | ID: wpr-922895

ABSTRACT

Mitochondria is involved in many important physiological activities such as energy supply, signal transduction, cell differentiation, etc., and plays an significant role in the occurrence and development of diseases. Using mitochondria as a target is a new strategy for cancer treatment. The use of nanotechnology to construct a mitochondrial targeted nano-drug delivery system can improve the solubility of traditional drugs, prolong the half-life of drugs in the body, increase the bioavailability and concentration of drugs at the tumor site, and reduce the toxic and side effects of drugs. It is expected to solve the resistance in the process of tumor treatment. This review focuses on the field of cancer treatment. Firstly, it introduces the mechanism of mitochondrial targeted nano-drug delivery system for cancer treatment. Secondly, it outlines the design ideas, classification and application research of mitochondrial targeted nano-drug delivery systems in the past five years. Finally, it expands the analysis of other studies that target mitochondria, such as bionic vectors, and presents its advantages and disadvantages, which provide a basis for in-depth research on drug delivery systems in the future.

6.
Protein & Cell ; (12): 26-46, 2022.
Article in English | WPRIM | ID: wpr-922494

ABSTRACT

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

7.
Rev. peru. biol. (Impr.) ; 28(2): e16669, abr.-jun 2021. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1280516

ABSTRACT

Resumen La variabilidad genética intrapoblacional de Vultur gryphus (cóndores andinos) de las regiones de Cusco y Apurímac fue evaluada mediante amplificación y secuenciación del ADN mitocondrial correspondientes a la región control y subunidad ribosomal 12S (D-Loop-ARNr12S), y a los genes Citocromo Oxidasa subunidad I (COI) y NADH deshidrogenasa subunidad II (ND2). El ADN se extrajo a partir de cálamos de plumas de muda de ejemplares en cautiverio y silvestres. Se analizaron los principales índices de diversidad genética como son: la diversidad haplotípica, la diversidad nucleotídica, el número promedio de diferencias nucleotídicas y el número de sitios polimórficos. La tasa de éxito de amplificación mediante PCR fue de 100% para las tres regiones de ADN analizadas. Se secuenció 600 pb de la región D-Loop-ARNr12S caracterizándose cuatro haplotipos, 704 pb del gen COI caracterizándose seis haplotipos y 1090 pb del gen ND2 caracterizándose cinco haplotipos. El gen COI presentó el mayor valor de diversidad haplotípica (Hd = 0.468), la región del gen D-Loop-ARNr12S presentó el mayor índice de diversidad nucleotídica (π = 0.00086), mientras que el gen COI presentó el mayor número promedio de diferencias nucleotídicas (K = 0.52615). Los resultados muestran bajos niveles de variabilidad genética en los genes mitocondriales de los cóndores andinos de la zona de estudio, que indicarían una población con estructura genética homogénea.


Abstract The intrapopulation genetic variability of Vultur gryphus (Andean condors) from Cusco and Apurimac regions was evaluated by amplification and sequencing of mitochondrial DNA corresponding to the control region and 12S ribosomal subunit (D-Loop-RNAr12S), Cytochrome Oxidase subunit I (COI) genes and NADH dehydrogenase subunit II (ND2) gene. DNA was extracted from the calamus of feathers recollected from captive and wild specimens. The main indices of genetic diversity such as the haplotype diversity, the nucleotide diversity, the average number of nucleotide differences and the number of polymorphic sites were analyzed. The PCR amplification success rate was 100% for the three mitochondrial amplified sequences. Four haplotypes were identified from the 600 bp sequenced of D-Loop-RNAr12S region; six haplotypes from the 704 bp sequenced of the COI gene; five haplotypes from the 1090 bp sequenced of the ND2 gene. The COI gene presented the highest haplotype diversity (Hd = 0.468), the D-Loop-RNAr12S region presented the highest index of nucleotide diversity (π = 0.00086), while the COI gene presented the highest average number of nucleotide differences (K = 0.52615). The results show low levels of genetic variability in the mitochondrial genes of the Andean Condor in the study area, indicating a population with a homogeneous genetic structure.

8.
Rev. argent. cardiol ; 89(2): 92-97, abr. 2021. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1356854

ABSTRACT

RESUMEN Introducción: Resultados de nuestro laboratorio sugieren que la disfunción mitocondrial en el corazón precede a la falla miocárdica asociada a la hiperglucemia sostenida. Objetivo: Estudiar los eventos tempranos que ocurren en las mitocondrias de corazón en un modelo de diabetes mellitus tipo 1. Materiales y métodos: Ratas Wistar macho fueron inyectadas con estreptozotocina (STZ; 60 mg/kg, ip) y sacrificadas 10 o 14 días posinyección. Se obtuvo la fracción mitocondrial de corazón. Resultados: El consumo de O2 en estado 3 en presencia de malato-glutamato (21%) o succinato (16%) y las actividades de los complejos I-III (27%), II-III (24%) y IV (22%) fueron menores en los animales diabéticos a los 14 días posinyección. Cuando los animales se sacrificaron al día 10, solo el consumo de O2 en estado 3 en presencia de sustratos del complejo I (23%) y su control respiratorio (30%) fueron menores en las ratas inyectadas con STZ, de acuerdo con una reducción en la actividad del complejo I-III (17%). Estos cambios se acompañaron de un aumento en las velocidades de producción de H2O2 (117%), NO (30%) y ONOO- (∼225%), en la expresión de mtNOS (29%) y en la [O2 -]ss (∼150%) y [NO]ss (∼30%), junto con una disminución de la actividad de la Mn-SOD (15%) y la [GSSG+GSH]mitocondrial (28%), sin cambios en la expresión de PGC-1α. Conclusión: La disfunción del complejo I y el aumento en la generación de H2O2, NO y ONOO- pueden considerarse señales subcelulares prodrómicas del deterioro de la función mitocondrial que precede a la disfunción cardíaca en la diabetes.


ABSTRACT Background: Previous results from our laboratory suggest that heart mitochondrial dysfunction precedes myocardial failure associated with sustained hyperglycemia. Purpose: The aim of this study was to analyze the early events that take place in heart mitochondria in a type 1 diabetes mellitus (DM) model. Methods: Male Wistar rats were injected with streptozotocin (STZ; 60 mg/kg, ip.) to induce DM. They were euthanized 10 or 14 days later and the heart mitochondrial fraction was obtained. Results: State 3 O2 consumption in the presence of malate-glutamate (21%) or succinate (16%), and complex I-III (27%), II-III (24%) and IV (22%) activities were lower in diabetic animals 14 days after STZ injection. When animals were euthanized at day 10, only state 3 O2 consumption sustained by complex I substrates (23%) and its corresponding respiratory control (30%) were lower in rats injected with STZ, in agreement with reduced complex I-III activity (17%). These changes were accompanied by increased H2O2 (117%), NO (30%) and ONOO- (~225%) production rates, mtNOS expression (29%) and O2 - (~150%) and NO (~30%) steady-state concentrations, together with a decrease in Mn-SOD activity (15%) and mitochondrial [GSSG+GSH] (28%), without changes in PGC-1α expression. Conclusion: Complex I dysfunction and increased H2O2, NO and ONOO- production rates can be considered subcellular prodromal signals of the mitochondrial damage that precedes myocardial dysfunction in diabetes.

9.
J. venom. anim. toxins incl. trop. dis ; 27: e20200183, 2021. graf
Article in English | LILACS, VETINDEX | ID: biblio-1287097

ABSTRACT

The COVID-19 pandemic brought attention to studies about viral infections and their impact on the cell machinery. SARS-CoV-2, for example, invades the host cells by ACE2 interaction and possibly hijacks the mitochondria. To better understand the disease and to propose novel treatments, crucial aspects of SARS-CoV-2 enrolment with host mitochondria must be studied. The replicative process of the virus leads to consequences in mitochondrial function, and cell metabolism. The hijacking of mitochondria, on the other hand, can drive the extrusion of mitochondrial DNA (mtDNA) to the cytosol. Extracellular mtDNA evoke robust proinflammatory responses once detected, that may act in different pathways, eliciting important immune responses. However, few receptors are validated and are able to detect and respond to mtDNA. In this review, we propose that the mtDNA and its detection might be important in the immune process generated by SARS-CoV-2 and that this mechanism might be important in the lung pathogenesis seen in clinical symptoms. Therefore, investigating the mtDNA receptors and their signaling pathways might provide important clues for therapeutic interventions.(AU)


Subject(s)
DNA/analysis , Genes, Mitochondrial , COVID-19 , Cytokines
10.
Chinese Journal of Nephrology ; (12): 583-590, 2021.
Article in Chinese | WPRIM | ID: wpr-911886

ABSTRACT

Objective:To evaluate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on lipid homeostasis and cellular injury of podocytes, and to clarify its mechanism.Methods:Twelve-week old C57BL/6 wild-type mice ( n=10) and PCSK9 knockout ( PCSK9 KO) mice ( n=10) were selected as the animal models. The renal tissues were taken after perfusion through heart. Mouse podocytes were transfected with PCSK9 siRNA to downregulate PCSK9 expression. BODIPY 493/503 staining was performed for evaluating lipid accumulation, and standard transmission electron microscopy (TEM) was used to observe the foot process of podocytes, the shape of mitochondria and lipid droplet in podocytes. TUNEL staining was carried out to evaluate cell apoptosis in glomerulus. The parameters about mitochondria function (key enzymes such as PGC-1α, CPT-1 and Acox-1) and apoptosis were quantified through qPCR and western blotting. Results:The lipid accumulation in glomerulus of PCSK9 KO mice were more serious than controls. The expression of PGC-1α protein and PGC-1α, CPT-1 and Acox-1 mRNA in PCSK9 KO mouse kidney tissues were decreased than controls (all P<0.05), and mitochondria swelling and cristae disappearance in podocytes of PCSK9 KO mice were observed. In PCSK9 KO group, the foot process of podocytes partially fused and disappeared, and the apoptosis index increased compared with the control group ( P<0.05). In vitro, compared with the control group, the lipid accumulation was more significant, transcription level of key enzymes related to mitochondrial function was decreased, mitochondrial structure was damaged and the apoptosis index was increased in cultured podocyte PCSK9 siRNA group (all P<0.05). Conclusions:PCSK9 is involved in the lipid homeostasis of podocytes. The decrease of PCSK9 results in the increase of intracellular lipid accumulation, accompanied by the mitochondrial structure damage and disfunction of podocytes, and leads to cell apoptosis.

11.
Article in Chinese | WPRIM | ID: wpr-911316

ABSTRACT

Objective:To evaluate the effect of TBK1 overexpression on hypoxia-reoxygenation (H/R) injury in isolated mouse cardiomyocytes subjected to high glucose and the relationship with mitochondrial autophagy.Methods:Normally cultured log-phase HL-1 mouse cardiomyocytes were inoculated in a 6-well plate at a density of 1×10 6 cells/ml and were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), high glucose group (group HG), high glucose and H/R group (group HG+ H/R), and TBK1 overexpression group (group TBK1). The cells were incubated in culture medium with 1% fetal bovine serum and 1% double antibody for 24 h when the cell density reached 50%.When the cell density reached 80%, pcDNA3.1 (+ ) was used as a vector to achieve TBK1 overexpression.The cells were cultured with high glucose medium (33 mmol/L) for 24 h, exposed to 94% N 2+ 5% CO 2+ 1% O 2 for 24 h in an incubator at 37℃ followed by 12 h reoxygenation in an incubator containing 5% CO 2 at 37°C to establish the model of H/R injury to cardiomyocytes subjected to high glucose.After reoxygenation, CCK-8 assay was used to detect cell viability, the activity of lactic dehydrogenase (LDH) in supernatant was detected using LDH kit, mitochondrial contents were determined using Mito-Tracter green fluorescent probe, and the expression of TBK1 and mitophagy-related proteins PINK1, Parkin, LC3B and P62 was detected by Western blot. Results:Compared with group C, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, mitochondrial contents were decreased, the expression of TBK1, PINK1, Parkin and LC3B was down-regulated, and the expression of P62 was up-regulated in HG group and HG+ H/R group ( P<0.05). Compared with group HG, the cell viability was significantly decreased, the activity of LDH in supernatant was increased, mitochondrial contents were decreased, the expression of TBK1, PINK1, Parkin and LC3B was down-regulated, and the expression of P62 was up-regulated in group HG+ H/R ( P<0.05). Compared with group HG+ H/R, the the cell viability was significantly increased, the activity of LDH in supernatant was decreased, mitochondrial contents were increased, the expression of TBK1, PINK1, Parkin and LC3B was up-regulated, and the expression of P62 was down-regulated in group TBK1 ( P<0.05). Conclusion:The mechanism by which TBK1 overexpression reduces the H/R injury is related to restoring mitophagy in isolated mouse cardiomyocytes subjected to high glucose.

12.
Article in Chinese | WPRIM | ID: wpr-911201

ABSTRACT

Objective:To investigate the relationship between the mechanism of exogenous hydrogen sulfide (H 2S)-induced reduction of apoptosis in neurons during focal cerebral ischemia-reperfusion (I/R) and PINK1/Parkin pathway-mediated mitochondrial autophagy in rats. Methods:Two hundred and sixteen healthy male Sprague-Dawley rats, aged 6-8 weeks, weighing 250-270 g, were divided into 4 groups ( n=54 each) using a random number table method: control group (group C), I/R group, H 2S group and H 2S plus 3-methyladenine (3-MA) group (H 2S+ 3-MA group). Focal cerebral ischemia was induced by middle cerebral artery occlusion in anesthetized rats.In group H 2S+ 3-MA, 3-MA 10 mg/kg was intraperitoneally injected at 15 min before the onset of reperfusion, while the equal volume of normal saline was given instead in the other groups.In H 2S and H 2S+ 3-MA groups, 0.25% NaSH (a donor of exogenous H 2S) 10 mg/kg was intraperitoneally injected at the onset of reperfusion, while the equal volume of normal saline was given instead in the other groups.At 1, 3 and 7 days of reperfusion, neural function was scored, and corner test (the percentage of left turn was calculated) was performed.Brains were removed and brain tissues were obtained for determination of the cerebral infarct size, Bax, Bcl-2 and caspase-3 positive cells, cell apoptosis, and expression of mitophagy-related protein microtubule-associated protein 1 light chain 3 (LC3), PINK1 and Parkin (by Western blot). The percentage of cerebral infarct size, rate of Bax, Bcl-2 and caspase-3 positive cells and apoptosis rate were calculated.The ratio of LC3-Ⅱexpression to LC3-Ⅰexpression (LC3-Ⅱ/LC3-Ⅰ) was also calculated. Results:Compared with group C, the neural function score was significantly decreased, the percentage of left turn, percentage of cerebral infarct size, rate of Bax, Bcl-2 and caspase-3 positive cells, apoptosis rate of neurons, and LC3-Ⅱ/LC3-Ⅰ were increased, and the expression of PINK1 and Parkin was up-regulated at each time point of reperfusion in group I/R ( P<0.05). Compared with group I/R, the neural function score and rate of Bcl-2 positive cells were significantly increased, the percentage of left turn, percentage of cerebral infarct size, rate of Bax and caspase-3 positive cells, and apoptosis rate of neurons were decreased, the expression of PINK1 and Parkin was up-regulated, and LC3-Ⅱ/LC3-Ⅰ were increased at each time point of reperfusion in group H 2S ( P<0.05), and no significant change was found in the parameters mentioned above in group H 2S+ 3-MA ( P>0.05). Compared with group H 2S, the neural function score and rate of Bcl-2 positive cells were significantly decreased, the percentage of left turn, percentage of cerebral infarct size, rate of Bax and caspase-3 positive cells, and apoptosis rate of neurons were increased, the expression of PINK1 and Parkin was down-regulated, and LC3-Ⅱ/LC3-Ⅰ was decreased at each time point of reperfusion in H 2S+ 3-MA group ( P<0.05). Conclusion:The mechanism by which exogenous H 2S inhibits apoptosis in neurons during focal cerebral I/R is related to enhancing mitochondrial autophagy mediated by the PINK1/Parkin pathway in rats.

13.
Article in Chinese | WPRIM | ID: wpr-910609

ABSTRACT

Mitochondrial dysfunction is closely related to the occurrence and development of benign and malignant diseases of the pancreas. Mitochondrial membrane of the respiratory chain electron transfer and energy transfer plays an important role in maintaining normal cellular function. When the respiratory chain was disrupted, the oxidative stress was increased in the cell, and produced a large number of oxide intermediate products which target mitochondrial protein, DNA, etc, lead to mitochondrial dysfunction finally induced acute pancreatitis, pancreatic cancer and other diseases. In addition, mitochondrial homeostasis plays an indispensable role in maintaining the normal function of islet cells. This paper reviewed the research status of mitochondrial dysfunction in pancreatic diseases.

14.
Article in Chinese | WPRIM | ID: wpr-910330

ABSTRACT

Objective:To investigate epithelial-mesenchymal transition and to explore the effects of mitochondrial dysfunction and increased expression of TGF-β1 pathway on epithelial-mesenchymal transition (EMT) in pancreatic adenocarcinoma after X-ray irradiation.Methods:Split-dose irradiations of total 40 Gy (2 Gy × 20 and 4 Gy × 10) of 6 MV X-rays were performed on PATU1 988 t cells. The migration of the cells were examined through transwell filter chambers. Real-time PCR was adopted to detect the expression of EMT-related factors E-cadherin, Vimentin, N-cadherin, and MMPs (MMP2 and MMP9), critical subunits of mitochondrial complex I, and TGF-β1. The expression of EMT-related factors and content of TGF-β1 was detected after carbonylcyanide-m-chlorophenylhydrazone(CCCP) treatment. Meanwhile, the migration potential of pancreatic cells was detected after small interfering RNA (siRNA) knockdown of the expression of TGF-β1.Results:After irradiation, the migration capacities of the cancer cells increased ( t=21.90, 35.64, P<0.05). The expression of N-cadherin ( t=4.42, 4.77, P<0.05), Vimentin ( t=4.57, 3.02, P<0.05), MMP2 ( t=7.27, 26.08, P<0.05), and MMP9 ( t=13.26, 7.29, P<0.05) all increased, while the expression of E-cadherin deceased ( t=8.37, 6.77, P<0.05). The expression of TGF-β1 ( t=90.49, 35.17, P<0.05) increased. The expression of TGF-β1 decreased with small interfering RNA, which paralleled the inhibition of the epithelial-mesenchymal transition and migration ( t=38.66, 11.54, P<0.05). Mitochondrial dysfunction was reflected by the decline in the membrane potential ( t=6.94, 29.71, P<0.05) and complex-related subunits. The expression of TGF-β1 ( t=47.93, P<0.05) and EMT-related factors further increased after mitochondrial function was destroyed ( t=16.51, P<0.05). Conclusions:Radiation-induced mitochondrial dysfunction can increase the expression of TGF-β1, which promotes epithelial-mesenchymal transition, and result in the migration of pancreatic cancer cell line.

15.
Journal of Chinese Physician ; (12): 1269-1274, 2021.
Article in Chinese | WPRIM | ID: wpr-909694

ABSTRACT

Parkinson′s disease (PD) is a neurodegenerative disease commonly found in middle-aged and elderly people. It is characterized by resting tremor, bradykinesia, myotonia, and abnormal posture gait. The main pathological changes were the loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies in the cytoplasm of the residual neurons. The main component of the Lewy bodies was α-synuclein. And why it causes the degeneration of dopaminergic neurons in the substantia nigra is not known. At present, most studies on Parkinson′s disease focus on the pathogenesis of the disease. More and more evidence shows that respiratory chain injury is a key feature of sporadic PD patients, and the proteins encoded by PD-related genes are related to the disorder of mitochondrial function. We believe that the important mechanism of the disease is impaired mitochondrial function due to environmental and (or) genetic inheritance. This article highlights new advances in mitochondrial dysfunction in Parkinson′s pathogenesis, including mitochondria and cell-mediated immunity, endoplasmic reticulum (ER)-mitochondrial axis, sirtuin-mediated mitochondrial stress response, and the role of microRNA in the etiology of PD. A deeper understanding of these mechanisms may provide inspiration for the development of new targeted therapies.

16.
International Journal of Surgery ; (12): 410-416, 2021.
Article in Chinese | WPRIM | ID: wpr-907453

ABSTRACT

Diabetic bladder dysfunction is one of the most common complications of urinary tract in diabetes. It is believed that the disorders of glucose metabolism, local tissue ischemia, superoxide-induced free radical production and axonal transport disorder are all involved in the development of diabetic bladder nerve dysfunction. Oxidative stress is believed to be the core mechanism of the above mentioned etiology. It may affect the transcription and translation process in the nucleus by interfering with the balance of intracellular oxidation and antioxidant, metabolism of neurotrophic factors and cellular signal transduction pathways, resulting in dysfunction of several important cellular pathways and decreased membrane stability. And eventually lead to nerve cell apoptosis. Therefore, controlling blood glucose, improving the microenvironment around dorsal root neurons, and protecting the stability of mitochondrial membrane may be potential methods for the treatment of diabetic bladder nerve dysfunction.

17.
Article in Chinese | WPRIM | ID: wpr-907321

ABSTRACT

Neural tube defects are a group of severe congenital malformations, including anencephaly, spina bifida, and encephalocele, which happen when neural tube fails to achieve proper closure during early embryogenesis.Mitochondria are an important site for biological oxidation and substance metabolism, as well as an important component in maintaining homeostasis of the intracellular environment.Mitochondria are also involved in the process of oocyte maturation, fertilization and embryonic development.Normal function of mitochondria is the key to the normal development of embryos.Therefore, mitochondrial dysfunction may be one of the mechanisms of neural tube closure failure.Slc25a32, SHMT2, MTHFD2/MTHFD2L, MTHFD1L and glycine cleavage system(GCS)are a series of key molecules of the mitochondrial one-carbon metabolic pathway.This paper reviews the research progress of mitochondrial dysfunction in the pathogenesis of neural tube malformation by starting from several key molecules and combining with the two main metabolic pathways of one-carbon metabolic chain and oxidative respiratory chain.

18.
Acta Pharmaceutica Sinica ; (12): 3243-3251, 2021.
Article in Chinese | WPRIM | ID: wpr-906845

ABSTRACT

This study aims at the critical role of P-glycoprotein (P-gp) in tumor drug resistance, taking advantage of the adenosine triphosphate (ATP) dependence of P-gp mediated drug transport and efflux across the cell membrane. Mitochondrial targeted calcium arsenite/doxorubicin (DOX) lipid nanoparticles were constructed via hydrothermal method and thin-film dispersion method for reversing tumor drug resistance. The results showed that the lipid nanoparticles were uniform in size and well dispersed with a mean particle size of (261 ± 7) nm, zeta potential of (-9.6 ± 1.3) mV. The DOX loading efficiency and encapsulation efficiency were 22.6% and 84.0%. The in vitro drug release profile was pH-dependent; the drug accumulation at mitochondria was significantly increased, which then caused overload of calcium and inhibition of P-gp and ATP, thereby reversing tumor drug resistance. The simultaneously released arsenite ion and DOX could synergistically kill the tumor cells. In summary, the lipid nanoparticles prepared in this study have uniform particle size, high drug loading efficiency and encapsulation efficiency, excellent colloidal stability, pH responsiveness, and impressive ability to reverse tumor drug resistance, which may hold great potential in further clinical applications.

19.
Article in Chinese | WPRIM | ID: wpr-906451

ABSTRACT

Objective:To observe the effects of Da Chaihutang on Cyclic adenosine monophosphate (cAMP)-response element binding protein (CREB)/peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1<italic>α</italic>) pathway in nutritionally obese rats and the protective mechanism on liver mitochondria. Method:A total of 120 8-week-old male SD rats were randomly divided into a control group (<italic>n</italic>=20) and an experimental group (<italic>n</italic>=100). The rats in the control group were fed on a normal diet, while those in the experimental group were administered with a high-fat feed. Successfully modeled rats were randomly divided into a model group, a positive drug (metformin) group, and low-, medium- and high-dose Da Chaihutang groups (4.25, 8.5, and 17 g∙kg<sup>-1</sup>, respectively), with 20 rats in each group. After treatment with Da Chaihutang, the body weight, Lee's index, liver mitochondrial membrane potential and mitochondrial ultrastructure, PGC-1<italic>α </italic>expression and CREB phosphorylation of each group were measured and compared. Result:Compared with the control group, the model group showed increased body weight and Lee's index (<italic>P</italic><0.01), whereas decreased mitochondrial membrane potential, PGC-1<italic>α</italic> expression, and CREB phosphorylation level (<italic>P</italic><0.01). As compared with the model group, Da Chaihutang significantly reduced the body weight and Lee's index of obese rats (<italic>P</italic><0.05, <italic>P</italic><0.01), enhanced liver mitochondrial membrane potential (<italic>P</italic><0.05, <italic>P</italic><0.01) to protect the integrity of mitochondrial structure, up-regulated PGC-1<italic>α</italic> expression and promoted CREB phosphorylation (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:Da Chaihutang protects the structure and function of mitochondria and inhibits weight gain in obese rats by activating the CREB/PGC-1<italic>α</italic> pathway.

20.
Article in Chinese | WPRIM | ID: wpr-905876

ABSTRACT

Objective:To develop the specific molecular markers of <italic>Codonopsis</italic> plants and better identify their germplasm resources considering the significant difference in active ingredients of Codonopsis Radix from various origins and producing areas. Method:Such bioinformatics software as Primer 5.0, NTSYS-pc 2.10e, and PopGene 32 were used for searching the simple sequence repeat (SSR) markers of <italic>C. minima </italic>chloroplast genome, <italic>C. tsinlingensis</italic> chloroplast, and <italic>C. lanceolata </italic>mitochondrial sequences, and 120 pairs of SSR primers were designed by Primer 5.0. Then 16 pairs of cpSSR primers and 10 pairs of mtSSR primers with good screening effect and high polymorphism were selected for analyzing the interspecific versatility of 20 samples. Result:The results showed that 66 cpSSR primer sites and 26 mtSSR sites were identified from the genome sequences, with 86.20% of single nucleotide, 6.9% of dinucleotide, and 6.9% of trinucleotide for <italic>C. minima </italic>chloroplast, 83.78% of single nucleotide,13.51% of dinucleotide, and 2.71% of trinucleotide for <italic>C. tsinlingensis</italic> chloroplast, and 46.15% of single nucleotide and 53.85% of dinucleotide for <italic>C. lanceolata </italic>mitochondria. As demonstrated by polymerase chain reaction (PCR) identification results, the developed 26 pairs of SSR primers had good applicability in the genus<italic> Codonopsis</italic>. The analysis by NTSYS-pc 2.10e revealed that the genetic similarity coefficients of 20 samples were within the range of 0.38-1.00, and they were divided into two subgroups at a threshold of 0.69. Four pairs of polymorphic primers were screened out in the diversity analysis of 20 samples using PopGene 32. The number of observed alleles (<italic>Na</italic>) was 12, and the effective number of alleles (<italic>Ne</italic>) ranged from 1.362 9 to 2.605 9. The percentage of polymorphic loci (PPL) at each site was 100%, and the average values of genetic parameters<italic> Ho</italic>, <italic>He</italic>, and <italic>I</italic> at each site were 0.555 8, 0.444 2, and 0.753 2, respectively, indicating high polymorphism at each site. The screened four pairs of primers were utilized for DNA fingerprinting of the 20 samples, and it was found that the DNA fingerprints enabled the identification of these 20 samples. Conclusion:This study has provided a molecular basis for the study of the genetic relationship between plants in species <italic>Codonopsis</italic> and the intraspecific genetic differentiation.

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