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1.
Acta Pharmaceutica Sinica B ; (6): 1500-1513, 2022.
Article in English | WPRIM | ID: wpr-929370

ABSTRACT

Artemisia annua is the main natural source of artemisinin production. In A. annua, extended drought stress severely reduces its biomass and artemisinin production while short-term water-withholding or abscisic acid (ABA) treatment can increase artemisinin biosynthesis. ABA-responsive transcription factor AabZIP1 and JA signaling AaMYC2 have been shown in separate studies to promote artemisinin production by targeting several artemisinin biosynthesis genes. Here, we found AabZIP1 promote the expression of multiple artemisinin biosynthesis genes including AaDBR2 and AaALDH1, which AabZIP1 does not directly activate. Subsequently, it was found that AabZIP1 up-regulates AaMYC2 expression through direct binding to its promoter, and that AaMYC2 binds to the promoter of AaALDH1 to activate its transcription. In addition, AabZIP1 directly transactivates wax biosynthesis genes AaCER1 and AaCYP86A1. The biosynthesis of artemisinin and cuticular wax and the tolerance of drought stress were significantly increased by AabZIP1 overexpression, whereas they were significantly decreased in RNAi-AabZIP1 plants. Collectively, we have uncovered the AabZIP1-AaMYC2 transcriptional module as a point of cross-talk between ABA and JA signaling in artemisinin biosynthesis, which may have general implications. We have also identified AabZIP1 as a promising candidate gene for the development of A. annua plants with high artemisinin content and drought tolerance in metabolic engineering breeding.

2.
Acta Pharmaceutica Sinica B ; (6): 511-531, 2022.
Article in English | WPRIM | ID: wpr-929312

ABSTRACT

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.

3.
Acta Pharmaceutica Sinica B ; (6): 2832-2844, 2022.
Article in English | WPRIM | ID: wpr-939930

ABSTRACT

Algae are a large group of photosynthetic organisms responsible for approximately half of the earth's total photosynthesis. In addition to their fundamental ecological roles as oxygen producers and as the food base for almost all aquatic life, algae are also a rich source of bioactive natural products, including several clinical drugs. Cytochrome P450 enzymes (P450s) are a superfamily of biocatalysts that are extensively involved in natural product biosynthesis by mediating various types of reactions. In the post-genome era, a growing number of P450 genes have been discovered from algae, indicating their important roles in algal life-cycle. However, the functional studies of algal P450s remain limited. Benefitting from the recent technical advances in algae cultivation and genetic manipulation, the researches on P450s in algal natural product biosynthesis have been approaching to a new stage. Moreover, some photoautotrophic algae have been developed into "photo-bioreactors" for heterologous P450s to produce high-value added pharmaceuticals and chemicals in a carbon-neutral or carbon-negative manner. Here, we comprehensively review these advances of P450 studies in algae from 2000 to 2021.

4.
Article in Chinese | WPRIM | ID: wpr-928159

ABSTRACT

The present study investigated the effect of emodin on the serum metabolite profiles in the chronic constriction injury(CCI) model by non-target metabolomics and explored its analgesic mechanism. Twenty-four Sprague Dawley(SD) rats were randomly divided into a sham group(S), a CCI group(C), and an emodin group(E). The rats in the emodin group were taken emodin via gavage once a day for fifteen days(50 mg·kg~(-1)) on the first day after the CCI surgery. Mechanical withdrawal threshold(MWT) and thermal withdrawal threshold(TWL) in each group were performed before the CCI surgery and 3,7, 11, and 15 days after surgery. After 15 days, blood samples were collected from the abdominal aorta. The differential metabolites were screened out by non-target metabolomics and analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG) and ingenuity pathway analysis(IPA). From the third day after CCI surgery, the MWT and TWL values were reduced significantly in both CCI group and emodin group, compared with the sham group(P<0.01). At 15 days post-surgery, the MWT and TWL values in emodin group increased significantly compared with the CCI group(P<0.05). As revealed by non-target metabolomics, 72 differential serum metabolites were screened out from the C-S comparison, including 41 up-regulated and 31 down-regulated ones, while 26 differential serum metabolites from E-C comparison, including 10 up-regulated and 16 down-regulated ones. KEGG analysis showed that the differential metabolites in E-C comparison were enriched in the signaling pathways, such as sphingolipid metabolism, arginine biosynthesis, glycerophospholipid metabolism, and tryptophan metabolism. IPA showed that the differential metabolites were mainly involved in the lipid metabolism-molecular transport-small molecule biochemistry network. In conclusion, emodin can exert an analgesic role via regulating sphingolipid metabolism and arginine biosynthesis.


Subject(s)
Analgesics/pharmacology , Animals , Arginine , Emodin/pharmacology , Neuralgia/metabolism , Rats , Rats, Sprague-Dawley , Sphingolipids
5.
Article in Chinese | WPRIM | ID: wpr-928007

ABSTRACT

Monoterpenes are widely used in cosmetics, food, medicine, agriculture and other fields. With the development of synthetic biology, it is considered as a potential way to create microbial cell factories to produce monoterpenes. Engineering Saccharomyces cerevisiae to produce monoterpenes has been a research hotspot in synthetic biology. In S. cerevisiae, the production of geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) is catalyzed by a bifunctional enzyme farnesyl pyrophosphate synthetase(encoded by ERG20 gene) which is inclined to synthesize FPP essential for yeast growth. Therefore, reasonable control of FPP synthesis is the basis for efficient monoterpene synthesis in yeast cell factories. In order to achieve dynamic control from GPP to FPP biosynthesis in S. cerevisiae, we obtained a novel chassis strain HP001-pERG1-ERG20 by replacing the ERG20 promoter of the chassis strain HP001 with the promoter of cyclosqualene cyclase(ERG1) gene. Further, we reconstructed the metabolic pathway by using GPP and neryl diphosphate(NPP), cis-GPP as substrates in HP001-pERG1-ERG20. The yield of GPP-derived linalool increased by 42.5% to 7.6 mg·L~(-1), and that of NPP-derived nerol increased by 1 436.4% to 8.3 mg·L~(-1). This study provides a basis for the production of monoterpenes by microbial fermentation.


Subject(s)
Fermentation , Geranyltranstransferase/genetics , Monoterpenes/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism
6.
Chinese Journal of Biotechnology ; (12): 1738-1752, 2022.
Article in Chinese | WPRIM | ID: wpr-927815

ABSTRACT

Anthocyanins are widely distributed water-soluble pigments that not only give the fruit colorful appearances, but also are important sources of natural edible pigments. In recent years, the interest on anthocyanins of solanaceous vegetables is increasing. This paper summarized the structure of anthocyanins and its biosynthetic pathway, the structural genes and regulatory genes involved in the biosynthesis of anthocyanins in solanaceous vegetables, as well as the environmental factors affecting the biosynthesis. This review may help clarify the synthesis and regulation mechanism of anthocyanins in solanaceous vegetables and make better use of anthocyanins for quality breeding of fruit colors.


Subject(s)
Anthocyanins/metabolism , Fruit/genetics , Gene Expression Regulation, Plant , Plant Breeding , Vegetables/genetics
7.
Chinese Journal of Biotechnology ; (12): 1408-1420, 2022.
Article in Chinese | WPRIM | ID: wpr-927789

ABSTRACT

Ergothioneine is a multifunctional physiological cytoprotector, with broad application in foods, beverage, medicine, cosmetics and so on. Biosynthesis is an increasingly favored method in the production of ergothioneine. This paper summarizes the new progress in the identification of key pathways, the mining of key enzymes, and the development of natural edible mushroom species and high-yield engineering strains for ergothioneine biosynthesis in recent years. Through this review, we aim to reveal the molecular mechanism of ergothioneine biosynthesis and then employ the methods of fermentation engineering, metabolic engineering, and synthetic biology to greatly increase the yield of ergothioneine.


Subject(s)
Antioxidants , Ergothioneine/metabolism , Fermentation , Metabolic Engineering
8.
Chinese Journal of Biotechnology ; (12): 1307-1321, 2022.
Article in Chinese | WPRIM | ID: wpr-927782

ABSTRACT

Tetrapyrrole compounds are a class of compounds with important functions. They exist in living organisms and have been widely used in agriculture, food, medicine, and other fields. The cumbersome process and high cost of chemical synthesis, as well as the shortcomings of unstable quality of animal and plant extraction methods, greatly hampered the industrial production and applications of tetrapyrrole compounds. In recent years, the rapid development of synthetic biology has provided new tools for microorganisms to efficiently synthesize tetrapyrrole compounds from renewable biomass resources. This article summarizes various strategies for the biosynthesis of tetrapyrrole compounds, discusses methods to improve its biosynthesis efficiency and future prospects, with the aim to facilitate the research on biosynthesis of tetrapyrrole compounds.


Subject(s)
Biomass , Plants/genetics , Synthetic Biology , Tetrapyrroles
9.
Chinese Journal of Biotechnology ; (12): 1004-1024, 2022.
Article in Chinese | WPRIM | ID: wpr-927759

ABSTRACT

Triterpenoid saponins are widely used in medicine, health cares, cosmetics, food additives and agriculture because of their unique chemical properties and rich pharmacological activities. UDP-dependent glycosyltransferases (UGTs) are the key enzymes involved in triterpenoid saponin biosynthesis, and play important roles in the diversity of triterpenoid saponin structures and pharmacological activities. This review summarized the UGTs involved in plant triterpenoid saponin biosynthesis based on the sources of UGTs and the types of receptors. Moreover, the application of UGTs in heterologous biosynthesis of triterpenoid saponins based on synthetic biology was also discussed.


Subject(s)
Glycosyltransferases/genetics , Plants , Saponins/chemistry , Triterpenes
10.
Chinese Journal of Biotechnology ; (12): 666-677, 2022.
Article in Chinese | WPRIM | ID: wpr-927735

ABSTRACT

Mucic acid is a hexaric acid that can be biosynthesized by oxidation of D-galacturonic acid, which is the main constituent of pectin. The structure and properties of mucic acid are similar to that of glucaric acid, and can be widely applied in the preparation of important platform compounds, polymers and macromolecular materials. Pectin is a cheap and abundant renewable biomass resource, thus developing a process enabling production of mucic acid from pectin would be of important economic value and environmental significance. This review summarized the structure and hydrolysis of pectin, the catabolism and regulation of D-galacturonic acid in microorganisms, and the strategy for mucic acid production based on engineering of corresponding pathways. The future application of mucic acid are prospected, and future directions for the preparation of mucic acid by biological method are also proposed.


Subject(s)
Hexuronic Acids/metabolism , Pectins/metabolism , Sugar Acids/metabolism
11.
Chinese Journal of Biotechnology ; (12): 632-649, 2022.
Article in Chinese | WPRIM | ID: wpr-927733

ABSTRACT

The redox biosynthesis system has important applications in green biomanufacturing of chiral compounds. Formate dehydrogenase (FDH) catalyzes the oxidation of formate into carbon dioxide, which is associated with the reduction of NAD(P)+ into NAD(P)H. Due to this property, FDH is used as a crucial enzyme in the redox biosynthesis system for cofactor regeneration. Nevertheless, the application of natural FDH in industrial production is hampered by low catalytic efficiency, poor stability, and inefficient coenzyme utilization. This review summarized the structural characteristics and catalytic mechanism of FDH, as well as the advances in protein engineering of FDHs toward improved enzyme activity, catalytic efficiency, stability and coenzyme preference. The applications of using FDH as a coenzyme regeneration system for green biomanufacturing of chiral compounds were summarized.


Subject(s)
Catalysis , Coenzymes/metabolism , Formate Dehydrogenases/metabolism , NAD/metabolism , Protein Engineering
12.
Chinese Journal of Biotechnology ; (12): 605-619, 2022.
Article in Chinese | WPRIM | ID: wpr-927731

ABSTRACT

Acarbose is widely used as α-glucosidase inhibitor in the treatment of type Ⅱ diabetes. Actinoplanes sp. is used for industrial production of acarbose. As a secondary metabolite, the biosynthesis of acarbose is quite complex. In addition to acarbose, a few acarbose structural analogs are also accumulated in the culture broth of Actinoplanes sp., which are hard to remove. Due to lack of systemic understanding of the biosynthesis and regulation mechanisms of acarbose and its structural analogs, it is difficult to eliminate or reduce the biosynthesis of the structural analogs. Recently, the advances in omics technologies and molecular biology have facilitated the investigations of biosynthesis and regulatory mechanisms of acarbose and its structural analogs in Actinoplanes sp.. The genes involved in the biosynthesis of acarbose and its structural analogs and their regulatory mechanism have been extensively explored by using bioinformatics analysis, genetic manipulation and enzymatic characterization, which is summarized in this review.


Subject(s)
Acarbose/metabolism , Diabetes Mellitus, Type 2/drug therapy , Genetic Techniques , Humans
13.
Article in English | WPRIM | ID: wpr-929247

ABSTRACT

The spread of antibiotic-resistant bacteria and exhausted drug leads render some infections untreatable now and in the future. To deal with these "new challenges", scientists tend to re-pick up "old antibiotics". Fusidane-type antibiotics have been known for nearly 80 years as potent antibacterial agents against gram-positive bacteria, especially Staphylococci, and represent the only triterpene-derived antibiotic class in clinical setting. These attractive characteristics have drawn renewed attention on fusidane-type antibiotics in recent decades. Isolation, characterization, biological evaluation, as well as chemical modifications of fusidane-type antibiotics are increasingly being reported. Combinatorial biosynthesis of this type of antibiotics has been successfully utilized not only for elucidating the biosynthetic pathways, but also for expanding their structural diversity. Some isolated and synthetic compounds exhibit comparable or even more potent biological activity than fusidic acid. This review provides an overview of progress on the studies of structure and biology of fusidane-type antibiotics from 1943 to April 2021. The informative structure-activity relationship is also highlighted.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteria , Biology , Structure-Activity Relationship
14.
Braz. j. biol ; 82: e232434, 2022. tab, graf
Article in English | LILACS | ID: biblio-1153465

ABSTRACT

Abstract Many pathogenic strains have acquired multidrug-resistant patterns in recent a year, which poses a major public health concern. The growing need for effective antimicrobial agents as novel therapies against multidrug-resistant pathogens has drawn scientist attention toward nanotechnology. Silver nanoparticles are considered capable of killing multidrug-resistant isolates due to their oligo-dynamic effect on microorganisms. In this research study NPs were synthesized using the gram-positive bacteria Lactobacillus bulgaricus and its activity against selected pathogenic strains. Lactobacillus bulgaricus pure cultures were isolated from raw milk and grown in "De Man, Rogasa, and Sharp" broth for synthesis of nanoparticles. Lactobacillus bulgaricus culture was centrifuged and Cell- free supernatant of it was employed with aqueous silvery ions and evaluated their antibacterial activities against bacterial strains i.e. Staphylococcus aureus, Staphylococcus epidermidis and Salmonella typhi using agar well diffusion assay. Antibiotic profiling against selected pathogenic strains were also conducted using disc diffusion method. The synthesis and characterization of silver nanoparticles were monitored primarily by the conversion of the pale-yellow color of the mixture into a dark-brown color and via ultraviolet-visible absorption spectroscopy and Scanning electron microscopy respectively. The result showed that that AgNPs with size (30.65-100 nm) obtained from Lactobacillus bulgaricus were found to exhibit antibacterial activities against selected bacterial strains. Taken together, these findings suggest that Lactobacillus bulgaricus has great potential for the production of AgNPs with antibacterial activities and highly effective in comparison to tested antibiotics.


Resumo Muitas cepas patogênicas adquiriram padrões multirresistentes nos últimos anos, o que representa um grande problema de saúde pública. A crescente necessidade de agentes antimicrobianos eficazes como novas terapias contra patógenos multirresistentes atraiu a atenção dos cientistas para a nanotecnologia. As nanopartículas de prata são consideradas capazes de matar isolados multirresistentes por causa de seu efeito oligodinâmico em microrganismos. Neste estudo de pesquisa, as NPs foram sintetizadas usando a bactéria Gram-positiva Lactobacillus bulgaricus e sua atividade contra cepas patogênicas selecionadas. Culturas puras de Lactobacillus bulgaricus foram isoladas do leite cru e cultivadas em caldo "De Man, Rogasa e Sharp" para síntese de nanopartículas. A cultura de Lactobacillus bulgaricus foi centrifugada, e o sobrenadante livre de células foi empregado com íons prateados aquosos, avaliando-se suas atividades antibacterianas contra cepas bacterianas, isto é, Staphylococcus aureus, Staphylococcus epidermidis e Salmonella typhi usando ensaio de difusão em poço de ágar. O perfil de antibióticos contra cepas patogênicas selecionadas também foi conduzido usando o método de difusão em disco. A síntese e a caracterização das nanopartículas de prata foram monitoradas principalmente pela conversão da cor amarelo-pálida da mistura em uma cor marrom-escura e por espectroscopia de absorção visível e ultravioleta e por microscopia eletrônica de varredura, respectivamente. O resultado mostrou que AgNPs com tamanho de 30,65-100 nm, obtidas de Lactobacillus bulgaricus, exibiram atividades antibacterianas contra cepas bacterianas selecionadas. Tomados em conjunto, esses achados sugerem que o Lactobacillus bulgaricus tem um grande potencial para a produção de AgNPs com atividades antibacterianas e altamente eficazes em comparação aos antibióticos testados.


Subject(s)
Lactobacillus delbrueckii , Metal Nanoparticles , Anti-Infective Agents , Silver/pharmacology , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology
15.
Mem. Inst. Oswaldo Cruz ; 117: e210157, 2022. graf
Article in English | LILACS-Express | LILACS | ID: biblio-1375918

ABSTRACT

BACKGROUND Leishmania parasites cause leishmaniasis that range from self-limiting cutaneous lesions to more serious forms of the disease. The search for potential drug targets focusing on biochemical and metabolic pathways revealed the sterol biosynthesis inhibitors (SBIs) as a promising approach. In this class of inhibitors is found ketoconazole, a classical inhibitor of 14α-methysterol 14-demethylase. OBJECTIVE The present study aimed to better understand the biological response of Leishmania (Leishmania) amazonensis promastigotes at the cellular level after ketoconazole treatment. METHODS Herein, techniques, such as fluorimetry, flow cytometry, fluorescence microscopy, electron and scanning microscopy were used to investigate the cellular structures and to identify organelles affected by ketoconazole treatment. FINDINGS The study demonstrated, for the first time, the effect of ketoconazole on mitochondrion functioning and its probable relationship to cell cycle and death on L. (L.) amazonensis promastigotes (IFLA/BR/67/PH8 strain). MAIN CONCLUSIONS Ketoconazole-induced mitochondrial damages led to hyperpolarisation of this single organelle and autophagic vacuoles formation, as a parasite survival strategy. These damages did not reflect directly on the parasite cell cycle, but drove the parasites to death, making them susceptible to ketoconazole treatment in in vitro models.

16.
Rev. chil. obstet. ginecol. (En línea) ; 86(6): 516-520, dic. 2021. tab
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1388692

ABSTRACT

INTRODUCCIÓN Y OBJETIVO: El rol de la testosterona exógena en la función sexual femenina ha sido estudiado durante muchos años, con resultados contradictorios. En el último tiempo se ha promovido el uso de pellets de testosterona como una solución para mejorar la libido femenina, la cognición, la fuerza muscular y los sistemas cardiovascular y óseo, e incluso evitar el envejecimiento. Por ello, revisamos las publicaciones para tratar de responder si esto es una moda o el tratamiento más innovador del último tiempo. MÉTODO: Se analizaron las bases de datos PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct y ResearchGate. RESULTADOS: De acuerdo con la evidencia, la mejor testosterona disponible es la transdérmica y debe ser usada solo en el trastorno del deseo sexual hipoactivo (TDSH). Los trabajos que evalúan los pellets de testosterona tienen sesgos metodológicos importantes. Si bien son útiles para mejorar la función sexual femenina, producen concentraciones plasmáticas suprafisiológicas de testosterona, por lo que no se puede establecer su seguridad a largo plazo. Tampoco hay datos suficientes que avalen su uso para mejorar el rendimiento cognitivo y el bienestar general, en el tratamiento de enfermedades cardiovasculares o en la prevención de enfermedad ósea. CONCLUSIONES: La testosterona solo se recomienda en el tratamiento del TDSH por vía transdérmica. No recomendamos el uso de pellets de testosterona para el tratamiento de la disfunción sexual ni como hormona antienvejecimiento, ya que no hay estudios consistentes sobre su seguridad, eficacia y efectos adversos a largo plazo.


INTRODUCTION AND OBJECTIVE: The role of exogenous testosterone in female sexual function has been studied for many years with contradictory results. In recent times, the use of testosterone pellets has been promoted as a solution to improve female libido, cognition, muscle strength, cardiovascular system, bone and even prevent aging. Therefore, we will review the publications in order to answer whether this is a fad or the most innovative treatment of recent times. METHOD: The databases PubMed/Medline, Trip Database, Cochrane, SciELO, Scopus, UpToDate, Ovid, ProQuest, Science Direct and ResearchGate were analyzed. RESULTS: So far, the evidence best testosterone available is transdermal testosterone and that it should be used only in hypoactive sexual desire disorder (HSDD). Papers evaluating testosterone pellets have significant methodological biases. While they are useful in improving female sexual function, they produce supra-physiological plasma levels of testosterone, so their long-term safety cannot be established. There is also insufficient data to support their use in improving cognitive performance and general well-being, treatment of cardiovascular disease or prevention of bone disease. CONCLUSIONS: Testosterone is only recommended for the tratment of HSDD via the transdermal route. We do not recommended the use of testosterone pellets for the treatment of sexual dysfunction or as an anti aging hormone, as there are no consistent studies on its safety, efficacy, and long-term adverse effects.


Subject(s)
Humans , Female , Testosterone/administration & dosage , Sexual Dysfunctions, Psychological/drug therapy , Drug Implants , Androgens/biosynthesis
17.
Electron. j. biotechnol ; 50: 68-76, Mar. 2021. ilus, tab, graf
Article in English | LILACS | ID: biblio-1292417

ABSTRACT

BACKGROUND: Jasmonic acid (JA) is a signal transducer molecule that plays an important role in plant development and stress response; it can also efficiently stimulate secondary metabolism in plant cells. RESULTS: RNA-Seq technology was applied to identify differentially expressed genes and study the time course of gene expression in Rhazya stricta in response to JA. Of more than 288 million total reads, approximately 27% were mapped to genes in the reference genome. Genes involved during the secondary metabolite pathways were up- or downregulated when treated with JA in R. stricta. Functional annotation and pathway analysis of all up- and downregulated genes identified many biological processes and molecular functions. Jasmonic acid biosynthetic, cell wall organization, and chlorophyll metabolic processes were upregulated at days 2, 6, and 12, respectively. Similarly, the molecular functions of calcium-transporting ATPase activity, ADP binding, and protein kinase activity were also upregulated at days 2, 6, and 12, respectively. Time-dependent transcriptional gene expression analysis showed that JA can induce signaling in the phenylpropanoid and aromatic acid pathways. These pathways are responsible for the production of secondary metabolites, which are essential for the development and environmental defense mechanism of R. stricta during stress conditions. CONCLUSIONS: Our results suggested that genes involved in flavonoid biosynthesis and aromatic acid synthesis pathways were upregulated during JA stress. However, monoterpenoid indole alkaloid (MIA) was unaffected by JA treatment. Hence, we can postulate that JA plays an important role in R. stricta during plant development and environmental stress conditions.


Subject(s)
Cyclopentanes/metabolism , Apocynaceae/genetics , Oxylipins/metabolism , Plant Growth Regulators/metabolism , Stress, Physiological , Flavonoids/biosynthesis , Base Sequence , Gene Expression , Environment , Transcriptome
18.
Arq. bras. cardiol ; 116(2): 315-322, fev. 2021. graf
Article in English, Portuguese | LILACS | ID: biblio-1152998

ABSTRACT

Resumo Fundamento A doxorrubicina está associada à cardiotoxicidade e à morbidade cardíaca tardia. O heme está relacionado ao stress oxidativo celular. Entretanto, sua regulação específica em cardiomiócitos sob os efeitos de doxorrubicina ainda não foi documentada. Objetivo Nosso objetivo é avaliar as alterações de enzimas limitantes de velocidade no caminho metabólico do heme sob o efeito de doxorrubicina. Métodos Cardiomiócitos H9c2 com doxorrubicina em concentrações diferentes (1, 2, 5, 10μM respectivamente). Os testes de PCR em tempo real e Western Blot foram usados para determinar a expressão de proteína e mRNA para quatro enzimas cruciais (ALAS1, ALAS2, HOX-1, e HOX-2) que regulam o metabolismo do heme celular, e os níveis de heme foram detectados por ELISA. Um p<0,01 foi considerado significativo. Resultados Observamos um padrão com alteração dependendo da dose nos níveis de heme nas células H9c2 com o nível mais alto na concentração de 5μM de doxorrubicina, o que ocorreu sincronicamente com o nível mais alto de regulação para cima de ALAS1, bem como as enzimas degenerativas HOX-1 e HOX-2 na expressão de proteína e mRNA. Em contraste, observamos que a ALAS2 foi regulada para baixo gradualmente, inversamente proporcional às concentrações de doxorrubicina. Conclusão O aumento da expressão de ALAS1 pode ter um papel na elevação do nível do heme quando o cardiomiócito H9c2 for exposto à doxorrubicina, e pode ser um alvo terapêutico para a toxicidade miocárdica induzida por doxorrubicina. (Arq Bras Cardiol. 2021; 116(2):315-322)


Abstract Background Doxorubicin is associated with cardiotoxicity and late cardiac morbidity. Heme is related to cellular oxidative stress. However, its specific regulation in cardiomyocytes under doxorubicin effects has not yet been documented. Objective This study seeks to evaluate the changing profiles of rate-limiting enzymes in the heme metabolism pathway under the effect of doxorubicin. Methods H9c2 cardiomyocytes were incubated with doxorubicin at different concentrations (1,2,5,10μM respectively). The real-time PCR and Western Blot were used to determine the mRNA and protein expression for four pivotal enzymes (ALAS1, ALAS2, HOX-1, and HOX-2) regulating cellular heme metabolism, as well as the levels of heme were detected by ELISA. p<0.01 was considered significant. Results This study observed a dose-dependent changing pattern in heme levels in H9c2 cells with the highest level at the 5μM concentration for doxorubicin, which occurred synchronously with the highest upregulation level of ALAS1, as well as the degradative enzymes, HOX-1, and HOX-2 in mRNA and protein expression. By contrast, ALAS2, contrary to the increasing concentrations of doxorubicin, was found to be progressively down-regulated. Conclusion The increase in ALAS1 expression may play a potential role in the heme level elevation when H9c2 cardiomyocyte was exposed to doxorubicin and may be a potential therapeutic target for doxorubicin-induced myocardial toxicity. (Arq Bras Cardiol. 2021; 116(2):315-322)


Subject(s)
Humans , Chagas Cardiomyopathy , Chagas Disease , Stroke Volume , Biomarkers , Ventricular Function, Left , Galectin 3
19.
Article in English | WPRIM | ID: wpr-906767

ABSTRACT

@#This study aimed to investigate the ameliorative effects of 60% ethanol elution fraction (ESMW) from Si Miao Wan on the hepatic lipid accumulation and its mechanism.TG kit, BODIPY fluorescence staining, QPCR, WB, oil red O staining, and AMPKα knockdown were used to detect the ability of ESMW to improve lipid accumulation in hepatocytes stimulated with free fatty acid.Furthermore, the effects of ESMW on the oral glucose tolerance, serum biochemical indexes, TG content in liver tissue, the expressions of mRNA and protein related to lipid metabolism in liver tissue were studied in mice fed with high fat diet to verify the mechanism of ESMW fraction on hepatic lipid accumulation.The results showed that ESMW inhibited lipid accumulation induced by free fatty acids by regulating AMPK signaling pathway, and that ESMW significantly improved the lipid metabolism of mice fed with high fat diet, with relation to AMPK signaling pathway.

20.
Article in Chinese | WPRIM | ID: wpr-921738

ABSTRACT

The terpenoids in Pogostemon cablin have complex structures and abundant pharmacological effects. Patchouli alcohol(PA) and pogostone(PO) have a high medicinal value by virtue of anti-tumor, anti-inflammatory, antibacterial, antioxidant, and other biological activities. Due to the low content of terpenoid metabolites in P. cablin, the study of biosynthesis and metabolism regulation can provide a biosynthetic basis for obtaining high-content terpenoids. In this study, key enzyme genes in biosynthesis, transcription factors in metabolism regulation, spatio-temporal expression of terpene synthase were reviewed, aiming to provide a reference for the development, protection, and utilization of P. cablin resources.


Subject(s)
Pogostemon/genetics , Terpenes , Transcription Factors/genetics
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