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1.
Chinese Journal of Endocrine Surgery ; (6): 90-94, 2023.
Article in Chinese | WPRIM | ID: wpr-989902

ABSTRACT

Objective:To explore the effects of sevoflurane (Sev) on proliferation and invasion of breast cancer cells.Methods:Normal human breast epithelial cell line MCF10A and human breast cancer cell line MCF7 were purchased. The expression level of sirtuin 2 (SIRT2) , ATP citrate lyase (ACLY) in breast cancer cells and acetylation level of ACLY were measured. Breast cancer cells were divided into the following groups: Control group, 2% SEV group, 4% SEV group, si-NC group, si-SIRT2 group, 4% SEV+si-NC group, 4% SEV+si-SIRT2 group, SIRT2 group, SIRT2+ACLY-WT group, SIRT2+ACLY-3KQ group, SIRT2+ACLY-3KQ+4% SEV group, si-ACLY group, si-ACLY+ACLY-WT group, si-ACLY+ACLY-3KQ group. MTT and Transwell assay were used to detect cell proliferation and invasion.Results:Compared with MCF-10A cells (1.00±0.15) , SIRT2 was low expressed in Control group cells (0.43±0.03) ( q=11.98, P<0.001) , SEV could induce the expression of SIRT2 ( F=88.71, P<0.001) . In addition, ACLY and ACLY-3K acetylation level were up-regulated in breast cancer cells (all P<0.05) . Knockdown of SIRT2 or overexpression of ACLY and ACLY-3KQ could promote the proliferation and invasion of MCF7 cells (all P<0.05) , while SEV, overexpression of SIRT2 or knockdown of ACLY showed the opposite effects (all P<0.05) . Conclusion:Sev may inhibit the proliferation and invasion of breast cancer cells through SIRT2, which may be related to the regulation of ACLY deacetylation.

2.
Journal of Zhejiang University. Medical sciences ; (6): 1-10, 2023.
Article in English | WPRIM | ID: wpr-1009938

ABSTRACT

OBJECTIVES@#To develop a prediction model for postoperative prognosis in patients with cholangiocarcinoma (CCA) based on the expression of silence information regulator 2 (SIRT2).@*METHODS@#The differential expression of SIRT2 between CCA and normal tissues was analyzed using TCGA and GEO databases. Gene set enrichment analysis (GSEA) was used to explore potential mechanisms of SIRT2 in CCA. The expression of SIRT2 protein in CCA tissues and normal tissues (including 44 pairs of specimens) was also detected by immunohistochemistry (IHC) staining in 89 resectable CCA patients who underwent surgical treatment in The First Affiliated Hospital of Bengbu Medical College between January 2016 and December 2021. The relationship between SIRT2 expression and clinicopathological characteristics and prognosis of CCA patients was analyzed. A survival prediction model for patients with resectable CCA was constructed with COX regression results, the calibration curve and the time-dependent receiver operating characteristic curve (ROC) were used to evaluate the performance of the constructed model, and the predictive power between this model and the AJCC/TNM staging system (8th Edition) was compared.@*RESULTS@#SIRT2 mRNA was overexpressed in CCA tissues as shown in TCGA and GEO databases. IHC staining showed that SIRT2 protein expression in CCA tissues was significantly higher than that in adjacent non-tumor tissues. GSEA results showed that elevated SIRT2 expression may be involved in multiple metabolism-related signaling pathway, such as fatty acid metabolism, oxidative phosphorylation, amino acid metabolism, etc. SIRT2 expression level was related to serum triglycerides level, tumor size and lymph node metastasis (all P<0.05). The survival analysis results showed that the patients with higher SIRT2 expression had a significant lower overall survival (OS) than patients with lower SIRT2 expression (P<0.05). Univariate COX regression analysis suggested that pathological differentiation, clinical stage, postoperative treatment and SIRT2 expression level were associated with the prognosis of CCA patients (all P<0.05). Multivariate regression analysis confirmed that clinical stage and SIRT2 expression level were independent predictors of OS in postoperative CCA patients (both P<0.05). A nomogram based on SIRT2 for prediction of survival in postoperative CCA patients was constructed. The C-index of the model was 0.675, and the area under the time-dependent ROC curve (AUC) for predicting survival in the first, second, and third years was 0.879, 0.778, and 0.953, respectively, which were superior to those of AJCC/TNM staging system (8th Edition).@*CONCLUSIONS@#SIRT2 is highly expressed in CCA tissues, which is associated with poor prognosis in patients with resectable CCA. The nomogram developed based on SIRT2 may have better predictive power than the AJCC/TNM staging system (8th Edition) in prediction of survival of postoperative CCA patients.

3.
Int. j. morphol ; 40(6): 1648-1655, dic. 2022. ilus, tab
Article in English | LILACS | ID: biblio-1421809

ABSTRACT

SUMMARY: The skin, located on the outermost part of the body, is always exposed to external stimuli such as sunlight. The exposure of skin to ultraviolet B (UVB) radiation from sunlight is known to be a major environmental factor in inducing photoaging. After exposure to UVB, an increase in reactive oxygen species can affect the expression and activity of many critical proteins depending on the duration and dose of the UVB radiation. Mammalian sirtuins (SIRTs), which are nicotinamide dinucleotide-dependent protein deacetylases, are well known for playing a role in cellular longevity. However, little is known about SIRT protein alterations in keratinocytes upon UVB irradiation according to SIRT subtypes. Therefore, in this study, the distribution of non-mitochondrial SIRT1, SIRT2, and SIRT6 proteins was investigated by immunofluorescence (IF) staining of the skin of SKH-1 mice (n=12) after UVB irradiation for 10 weeks. After UVB irradiation for 10 weeks, the IF of both SIRT1 and SIRT6 was significantly increased in the UVB-irradiated mice group (UG), but the difference in SIRT2 IF was not statistically significant between the control group (CG) and the UG. The translocation of both SIRT1 and SIRT6 IF from the nucleus to the cytoplasm of keratinocytes was observed in the upper epidermis of the UG, whereas SIRT2 IF was localized in the cytoplasm of keratinocytes in the epidermis in both the CG and the UG. The translocation of SIRT1 and SIRT6 IF from the nucleus to the cytoplasm of keratinocytes may account for the physiologically protective action of keratinocytes against UVB irradiation. However, the exact role of SIRT1 and SIRT6 translocation in keratinocytes, where SIRT1 and SIRT6 shuttle from the nucleus to the cytoplasm, is not well known. Therefore, further studies are needed to understand the molecular mechanisms of SIRT1 and SIRT6 translocation in keratinocytes upon UVB irradiation.


La piel, situada en la parte más externa del cuerpo, está siempre expuesta a estímulos externos como la luz solar. Se sabe que la exposición de la piel a la radiación ultravioleta B (UVB) de la luz solar es un factor ambiental importante en la inducción del fotoenvejecimiento. Después de la exposición a los rayos UVB, un aumento en las especies reactivas de oxígeno puede afectar la expresión y la actividad de muchas proteínas críticas según la duración y la dosis de la radiación UVB. Las sirtuinas de mamíferos (SIRT), que son proteínas desacetilasas dependientes de dinucleótidos de nicotinamida, son bien conocidas por desempeñar un papel en la longevidad celular. Sin embargo, se sabe poco sobre las alteraciones de la proteína SIRT en los queratinocitos tras la irradiación UVB según los subtipos de SIRT. Por lo tanto, en este estudio, se investigó la distribución de las proteínas SIRT1, SIRT2 y SIRT6 no mitocondriales mediante tinción de inmunofluorescencia (IF) de la piel de ratones SKH-1 (n = 12), después de la irradiación con UVB durante 10 semanas. Posterior a la irradiación, el IF de SIRT1 y SIRT6 aumentaron significativamente en el grupo de ratones irradiados con UVB (UG), pero la diferencia en SIRT2 IF no fue estadísticamente significativa entre el grupo control (CG) y el UG. La translocación de SIRT1 y SIRT6 IF desde el núcleo al citoplasma de los queratinocitos se observó en la epidermis superior de la UG, mientras que SIRT2 IF se localizó en el citoplasma de los queratinocitos en la epidermis, tanto en el GC, como en la UG. La translocación de SIRT1 y SIRT6 IF del núcleo al citoplasma de los queratinocitos puede explicar la acción protectora fisiológica de estos contra la radiación UVB. Sin embargo, el papel exacto de la translocación de SIRT1 y SIRT6 en los queratinocitos, donde SIRT1 y SIRT6 se trasladan desde el núcleo al citoplasma, no se conoce bien. Por lo tanto, se necesitan más estudios para comprender los mecanismos moleculares de la translocación SIRT1 y SIRT6 en los queratinocitos tras la irradiación UVB.


Subject(s)
Animals , Male , Mice , Ultraviolet Rays , Keratinocytes/radiation effects , Sirtuins/radiation effects , Time Factors , Skin Aging , Fluorescent Antibody Technique , Sirtuins/analysis
4.
Chinese Pharmacological Bulletin ; (12): 1512-1518, 2021.
Article in Chinese | WPRIM | ID: wpr-1014269

ABSTRACT

Aim To investigate the mechanisms that propofol inhibits alcohol-induced liver injury in C57 mice. Methods HE and oil red staining methods were used to measure the injury and lipid accumulation rates in liver. Immunofluorescence (IF) was used to identify the colocalization rate of mitochondria and LC3. ALT and AST tests were used to identify the liver injury level. Molecular docking experiment was used to predict the target protein of propofol. Western blot and immunohistochemistry (IHC) experiments were used to detect SIRT2 protein level. Results Propofol could significantly attenuate alcohol-induced high ALT/AST level, lipid accumulation, and enhance mitophagy level. According to molecular docking and Western blot experiments, propofol had high correlation with SIRT2 protein, and propofol could rescue alcohol-induced low expression level of SIRT2 protein. In addition, sirReal2 (an inhibitor of SIRT2) could significantly inhibit the protective effects of propofol in mouse liver. Con-clusion Propofol could protect against alcohol-induced liver injury through SIRT2 protein to enhance mitophagy level.

5.
Journal of Shanghai Jiaotong University(Medical Science) ; (12): 848-855, 2019.
Article in Chinese | WPRIM | ID: wpr-752020

ABSTRACT

Objective·To investigate the role of mitochondrial solute carrier family 25 member 13 (SLC25A13) on breast cancer development.Methods·SLC25A13 mRNA and protein expressions in invasive breast cancer tissues and normal breast tissues were from The Cancer Genome Atlas (TCGA) breast cancer dataset. Survival analysis was conducted online by Kaplan-Meier software. MCF-7 cell line was used for in vitro cell assay.Knockdown of SLC25A13 and sirtuin 2 (SIRT2) were conducted by siRNA transfection. Cell viability was measured with trypan blue exclusion. Cell cycle arrest was determined by flow cytometry. The mRNA expression of SLC25A13 and P27 were detected by quantitative PCR. The protein level of SLC25A13, P27 and SIRT2 were detected by Western blotting. Protein half-life of P27 was assessed by Western blotting after ycloheximide treatment. Results·SLC25A13 was up-regulated in invasive breast cancer tissues. High expression of SLC25A13 correlated with poor overall survival and breast cancer recurrence. SLC25A13 knockdown inhibited MCF-7 cell cycle progression. P27 and SIRT2 both accumulated after SLC25A13 knockdown. P27 accumulation resulted from prolonged protein half-life. Knockdown of SIRT2 restored cell cycle arrest as well as P27 accumulation caused by SLC25A13 silencing. Conclusion·High expression of SLC25A13 may promote cell cycle progression via SIRT2 in breast cancer development.

6.
Journal of Shanghai Jiaotong University(Medical Science) ; (12): 848-855, 2019.
Article in Chinese | WPRIM | ID: wpr-843375

ABSTRACT

Objective:To investigate the role of mitochondrial solute carrier family 25 member 13 (SLC25A13) on breast cancer development. Methods:SLC25A13 mRNA and protein expressions in invasive breast cancer tissues and normal breast tissues were from The Cancer Genome Atlas (TCGA) breast cancer dataset. Survival analysis was conducted online by Kaplan-Meier software. MCF-7 cell line was used for in vitro cell assay. Knockdown of SLC25A13 and sirtuin 2 (SIRT2) were conducted by siRNA transfection. Cell viability was measured with trypan blue exclusion. Cell cycle arrest was determined by flow cytometry. The mRNA expression of SLC25A13 and P27 were detected by quantitative PCR. The protein level of SLC25A13, P27 and SIRT2 were detected by Western blotting. Protein half-life of P27 was assessed by Western blotting after cycloheximide treatment. Results:SLC25A13 was up-regulated in invasive breast cancer tissues. High expression of SLC25A13 correlated with poor overall survival and breast cancer recurrence. SLC25A13 knockdown inhibited MCF-7 cell cycle progression. P27 and SIRT2 both accumulated after SLC25A13 knockdown. P27 accumulation resulted from prolonged protein half-life. Knockdown of SIRT2 restored cell cycle arrest as well as P27 accumulation caused by SLC25A13 silencing. Conclusion:High expression of SLC25A13 may promote cell cycle progression via SIRT2 in breast cancer development.

7.
Experimental Neurobiology ; : 537-546, 2019.
Article in English | WPRIM | ID: wpr-763774

ABSTRACT

Silent information regulator 2 (Sirtuin2 / SIRT2) is a NAD⁺-dependent deacetylase that regulates the cellular oxidative stress response. It modulates transcriptional silencing and protein stability through deacetylation of target proteins including histones. Previous studies have shown that SIRT2 plays a role in mood disorders and hippocampus-dependent cognitive function, but the underlying neurobiological mechanism is poorly understood. Here, we report that chronic stress suppresses SIRT2 expression in the hippocampus. Molecular and biochemical analyses indicate that the stress-induced decrease in the SIRT2 expression downregulates synaptic plasticity-related genes in the hippocampus through the increase of euchromatic histone-lysine N-methyltransferase 2 (Ehmt2) (also known as G9a). shRNA-mediated knockdown of SIRT2 in the dentate gyrus alters the expression of synaptic plasticity-related genes in a way similar to those induced by chronic stress, and produces depression-like behaviors. Our results indicate that SIRT2 plays an important role in the response to stress, thereby modulating depression-like behaviors.


Subject(s)
Cognition , Dentate Gyrus , Depression , Down-Regulation , Hippocampus , Histone-Lysine N-Methyltransferase , Histones , Mood Disorders , Neuronal Plasticity , Oxidative Stress , Protein Stability , Up-Regulation
8.
Journal of Shanghai Jiaotong University(Medical Science) ; (12): 1247-1251, 2018.
Article in Chinese | WPRIM | ID: wpr-843598

ABSTRACT

Silence information regulators (sirtuins) are highly conserved nicotinamide adenine dinucleotide (NAD+) dependent histone deacetylases, which play important roles in the process of aging, metabolism, apoptosis, gene transcription, and inflammation. There are seven kinds of sirtuins in mammals, SIRT1-SIRT7. These proteins have different subcellular localization and play diverse roles in metabolism. SIRT2, one of the members of sirtuins family, is mainly located in the cytoplasm and participates in the cell cycle control, oxidative stress and glycolipid metabolism. In addition, the expression level of SIRT2 has been widely associated with the development of cancers, including hepatocellular carcinoma. SIRT2 possesses a dual role in tumorigenesis, with both tumor-promoting and tumor-suppressing function. However, the mechanisms in which SIRT2 plays the roles in cancer are still controversial. In this review, the conflicting roles of SIRT2 in the tumorigenesis and development of hepatocellular carcinoma were mainly discussed.

9.
Acta Pharmaceutica Sinica ; (12): 1259-1270, 2018.
Article in Chinese | WPRIM | ID: wpr-779996

ABSTRACT

As a post-translational modification, protein acetylation plays an important role in the regulation of apoptosis, mitochondriopoiesis, lipid metabolism and cellular stress response. The imbalance of acetylation and deacetylation has been blamed for the tumorigenesis and malignant progression, which is gradually considered as a promising therapeutic target. Mammalian sirtuins, a NAD+ dependent class Ⅲ HDACs, are closely related to the development of aging, tumor, diabetes, obesity and neurodegenerative diseases. To provide a theoretical basis for the development of new anti-tumor drugs and the treatment of malignant tumors, this paper is prepared to focus on the irreplaceable role of sirtuins in tumor evolution:maintaining genomic stability, regulating energy metabolism, and facilitating tumor cells stemness. The modulator and pathways of sirtuins family and the research progress of agonists and inhibitors are also reviewed. The functions of SIRT2 in resistance, proliferation and metastasis have been highlighted.

10.
Chinese Journal of Pathophysiology ; (12): 1209-1213, 2015.
Article in Chinese | WPRIM | ID: wpr-463101

ABSTRACT

[ ABSTRACT] AIM:To compare the expression of SIRT2 in ovarian surface epithelial ( OSE) cell line and serous ovarian carcinoma ( SOC) cell lines, and to investigate the effects of SIRT2 on the cell proliferation, migration and inva-sion.METHODS:The expression levels of SIRT2 in the OSE cell line and the SOC cell lines were determined by Western blot.The SIRT2 siRNAs and overexpression construct were designed and verified.Transient transfection of SIRT2 siRNAs or overexpression construct was performed, and the effect of SIRT2 on the cell proliferation, migration and invasion was e-valuated.RESULTS:SIRT2 levels in the 5 strains of SOC cell lines were significantly lower than that in the OSE cell line.SIRT2 knockdown in HOSEpiC cells significantly enhanced the ability of cell colony formation and accelerated the cell growth rate.On the contrary, overexpression of SIRT2 in HO8910 cells dramatically repressed the number of cell colonies and cell activity.SIRT2 significantly changed the ability of ovarian cell migration.Knockdown of SIRT2 facilitated the cell invasion.CONCLUSION:The expression of SIRT2 in the SOC cells is significantly down-regulated.In the OSE cells, SIRT2 acts as a tumor suppressor and mediates the inhibition of cell proliferation, migration and invasion.

11.
Journal of the Korean Geriatrics Society ; : 27-33, 2012.
Article in Korean | WPRIM | ID: wpr-63151

ABSTRACT

BACKGROUND: Studies on surtuin2 (SIRT2) proteins, particularly those focusing on the nervous system, have not been intensively done. Furthermore, neither the types of neural cells involved nor the changes in SIRT2 expression in each type have been clearly elucidated. In the present study, we used morphological techniques such as the double immunohistochemical study to assess the changes in the expressions of SIRT2 proteins in the rat brain during the aging process. METHODS: The immunohistochemical analyses employing anti-SIRT2, NeuN and GFAP antibodies were performed on 8-week and 24-month post-natal rat brains. Immunostained samples were observed under fluorescent microscopy. RESULTS: In the hippocampus of the 8-week old rat brains, most of the SIRT2 immunoreactivities (IRs) were localized in the GFAP-positive astrocytes. Contrastingly, the 24-month old rat brains showed aging-related changes- the SIRT2 IRs were highly increased in the NeuN-positive neurons, unlike in the 8-week old brains, which only showed low SIRT2 IRs. In samples representing the same age, the increase of SIRT2 IRs in the astrocytes was not as remarkable as in the neurons. CONCLUSION: Although previous studies have found increased SIRT2 in aged brains, they could not determine the type of neural cells responsible for such changes. Significantly, the data derived from the present study demonstrated that increased SIRT2 in aged brains was caused mainly by changes to the protein expression in neurons. Considering that SIRT2 is known to be related to the anti-aging process of cells, highly expressed SIRT2 in neurons might play a role in inhibiting the aging of the central nervous system.


Subject(s)
Aged , Animals , Humans , Rats , Aging , Antibodies , Astrocytes , Brain , Central Nervous System , Hippocampus , Microtubules , Nervous System , Neurons , Proteins
12.
Chinese Journal of Cellular and Molecular Immunology ; (12): 970-972, 2009.
Article in Chinese | WPRIM | ID: wpr-622111

ABSTRACT

AIM:To construct eukaryotic expression vector of Sirt2 and detect its expression in HEK293 cells. METHODS: Total RNA was isolated from brain tissue of a-dult SD rat. A 1 130 bp fragment containing the coding region of Sirt2 was amplified by RT-PCR and the resulting PCR product was subcloned into PMD20-T vector and se-quenced. Coding region of Sirt2 was generated with PCR by using the PMD20-T-Sirt2 as template, the amplified PCR fragment was inserted into the EcoR I and Hind Ⅲ sites of the pcDNA3. 1myc-his(-)A expression vector, and the sequence was confirmed by DNA sequencing. The expression of new construct pcDNA3.1 myc-his(-) A-Sirt2 in HEK293 cells was detected by immunofluorescence. RESULTS: The full length coding region of Sirt2 was obtained and confirmed by sequencing, the expression of Sirt2 was detected successfully in HEK293 cells. CONCLUSION: The eukaryotic expression vector of Sirt2 has been successfully constructed, which will provide a useful tool for designing an in-depth investigation of the role of Sirt2.

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