SIRT1, 2, 3 protect mouse oocytes from postovulatory aging

Zhang, Teng; Zhou, Yang; Li, Li; Wang, Honghui; Ma, Xue‐Shan; Qian, Weiping; Shen, Wei; Schatten, Heide; Sun, Qing‐Yuan

doi:10.18632/aging.100911

Cited by 81 publications

(77 citation statements)

References 42 publications

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“…The changes in glycolytic markers that we observed in the early premalignant colorectal mucosal field are consistent with changes that have been described in CRC, and these changes would be expected to promote increased glycolysis and shunting of glycolytic intermediates into anabolic pathways [11, 22, 25, 26, 29]. Consistent with an early Warburg Effect, our findings suggest an early increase in glucose uptake ( GLUT1 ) and pyruvate fermentation into lactate ( LDHA ).…”

Section: Discussionsupporting

confidence: 90%

Metabolic reprogramming of the premalignant colonic mucosa is an early event in carcinogenesis

et al. 2017

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BackgroundColorectal cancer (CRC) is the second leading cause of cancer-related mortality in the United States. There is an increasing need for the identification of biomarkers of pre-malignant and early stage CRC to improve risk-stratification and screening recommendations. In this study, we investigated the possibility of metabolic and mitochondrial reprogramming early in the pre-malignant colorectal field.MethodsRectal biopsies were taken from 81 patients undergoing screening colonoscopy, and gene expression of metabolic and mitochondrial markers were assessed using real time quantitative PCR. Validation studies were performed in two different animal models of colon carcinogenesis: Pirc rats and AOM-treated rats.ResultsWe found evidence of a Warburg effect in the normal-appearing rectal mucosa of patients harboring precancerous lesions elsewhere in the colon compared to control patients, with a significant increase in HIF1a, SLC2A1 (referred to as GLUT1), PKM2, and LDHA. We also found evidence of early mitochondrial changes in the colorectal field of patients harboring pre-cancerous lesions, with significantly increased mitochondrial gene expression of DRP1 (fission), OPA1 (fusion), PGC1-a (biogenesis), UCP2 (uncoupling) and mtND1 (copy number). Similar results were observed in the two different animal models.ConclusionsThese results demonstrate for the first time evidence of early Warburg-like metabolic changes as well as changes in mitochondrial function, dynamics and mtDNA copy number in endoscopically normal premalignant colorectal mucosal field. These findings provide an opportunity for the development of metabolic biomarkers that could be used for improving screening recommendations and risk-stratification. This also provides a potential target for novel chemopreventive strategies in the pre-malignant colorectal field.

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Section: Discussionsupporting

confidence: 90%

Metabolic reprogramming of the premalignant colonic mucosa is an early event in carcinogenesis

et al. 2017

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“…Mammals have 7 members (Sirt1-Sirt7) displayed differential cellular localization and function in numerous physiologic processes. 15 Among them, Sirt3 is localized in mitochondria and controls the acetylation status of almost 80»90% of mitochondrial proteins. 16 It regulates the production of ROS via the electron transport chain, as well as the detoxification of ROS through activation of antioxidant enzymes.…”

Section: Introductionmentioning

confidence: 99%

“…16 It regulates the production of ROS via the electron transport chain, as well as the detoxification of ROS through activation of antioxidant enzymes. 15,17,18 Recent studies highlight the critical role of Sirt3 in modulating ROS homeostasis in response to caloric restriction. Sirt3 is able to directly deacetylates isocitrate dehydrogenase 2 (IDH2), increasing the levels of NADPH and thereupon protecting cells from oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Sirt3-dependent deacetylation of SOD2 plays a protective role against oxidative stress in oocytes from diabetic mice

et al. 2017

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Maternal diabetes has been demonstrated to adversely affect oocyte quality in mouse oocytes. However, the potential molecular mechanisms are poorly understood. Here, we established a type I diabetic mouse model and detected the increased reactive oxygen species (ROS) levels and decreased Sirt3 expression in oocytes from diabetic mice. Furthermore, we found that forced expression of Sirt3 in diabetic oocytes significantly attenuates such an excessive production of ROS. The acetylation status of lysine 68 of superoxide dismutase (SOD2K68) is dependent on Sirt3 in oocytes. In line with this, SOD2K68 acetylation levels were markedly increased in diabetic oocytes, and Sirt3 overexpression could effectively suppress this tendency. Importantly, the deacetylation-mimetic mutant SOD2K68R is capable of partly preventing the oxidative stress in oocytes from diabetic mice. In conclusion, our findings support a model where Sirt3 plays a protective role against oxidative stress in oocytes exposed to maternal diabetes through deacetylating SOD2K68.

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“…A handful of studies have reported that postovulatory aging is highly correlated with a variety of defects in oocytes, including precocious release of cortical granules, zona pellucida hardening, spindle/chromosome abnormalities, weakened fertilization ability, and abnormal development of embryos and fetuses (5)(6)(7)(8)(9). In addition, postovulatory aging is accompanied by diverse molecular, cellular, and biochemical changes, such as dysfunction of mitochondria, generation of reactive oxygen species (ROS), reduced maturation-promoting factor activities, decreased expression of antiapoptotic factor B-cell lymphoma 2 (BCL-2), activation of caspase-3, and changes in epigenetic modifications (4,(10)(11)(12). These aging-induced deleterious changes have the potential to impair oocyte quality, thereby adversely affecting fertilization and subsequent embryo development.…”

mentioning

confidence: 99%

Postovulatory aging causes the deterioration of porcine oocytes via induction of oxidative stress

et al. 2018

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Negative effects of postovulatory aging on fertilization ability and subsequent embryo development have been reported in rodents; however, the molecular and cellular changes during this process have not been fully defined. Here, we used porcine oocytes, a model that is physiologically and developmentally similar to humans, to explore the molecular mechanisms that underlie how postovulatory aging affects oocyte quality and fertilization capacity. We found that postovulatory aging caused the morphologic change of porcine oocytes by exhibiting the incompact expansion of cumulus cells and an increased occurrence of fragmentation. Aging also impaired oocyte quality by disrupting organelle structures, including the spindle assembly, actin polymerization, and mitochondrial integrity. Moreover, postovulatory aging led to the abnormal distribution of cortical granules and ovastacin, which, in turn, resulted in defective sperm binding and consequently compromised fertilization potential. Of note, we observed that postovulatory aging induced oxidative stress with a high level of reactive oxygen species and apoptotic rate in oocytes, thereby resulting in the deterioration of critical factors in the maintenance of oocyte quality and fertilization capacity. Taken together, our findings demonstrate that postovulatory aging perturbs a variety of molecular and cellular changes in porcine oocytes by inducing oxidative stress.-Miao, Y., Zhou, C., Cui, Z., Zhang, M., ShiYang, X., Lu, Y., Xiong, B. Postovulatory aging causes the deterioration of porcine oocytes via induction of oxidative stress.

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SIRT1, 2, 3 protect mouse oocytes from postovulatory aging

Cited by 81 publications

References 42 publications

Metabolic reprogramming of the premalignant colonic mucosa is an early event in carcinogenesis

Metabolic reprogramming of the premalignant colonic mucosa is an early event in carcinogenesis

Sirt3-dependent deacetylation of SOD2 plays a protective role against oxidative stress in oocytes from diabetic mice

Postovulatory aging causes the deterioration of porcine oocytes via induction of oxidative stress

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