SIRT7 functions in redox homeostasis and cytoskeletal organization during oocyte maturation

Gao, Min; Li, Xiaoyan; He, Yongfu; Han, Longsen; Qiu, Danhong; Li, Ling; Liu, Honglin; Liu, Jianguo; Gu, Ling

doi:10.1096/fj.201800078rr

Cited by 32 publications

(29 citation statements)

References 52 publications

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“…In some inflammatory-related lung diseases, activated inflammatory cells like neutrophils and macrophages are thought to release considerable amounts of ROS, which in turn promote inflammation and trigger the development of other related diseases [29]. SIRT7 overexpression suppressed NO and ROS secretion in LPS-treated DCMECs, indicating that SIRT7 can suppress the initiation of inflammation by inhibiting NO and ROS production under normal conditions, which is consistent with a previous work [30]. A recent study demonstrated that SIRT7 is also involved in the regulation of mitochondrial homeostasis by deacetylating GABP β 1, which is important in regulating mitochondrial genes [31].…”

Section: Discussionsupporting

confidence: 90%

SIRT7 Regulates Lipopolysaccharide-Induced Inflammatory Injury by Suppressing the NF-κB Signaling Pathway

Chen

et al. 2019

Oxidative Medicine and Cellular Longevity

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Mastitis has severely affected the cattle industry worldwide and has resulted in decreased dairy production and cattle reproduction. Although prevention and treatment methods have been implemented for decades, cattle mastitis is still an intractable disease. Sirtuin 7 (SIRT7) is an NAD+-dependent deacetylase that is involved in various biological processes, including ribosomal RNA synthesis and protein synthesis, DNA damage response, metabolism, and tumorigenesis. However, whether SIRT7 participates in inflammation remains unknown. Our results revealed that SIRT7 is downregulated in tissue samples from mastitic cattle. Therefore, we isolated dairy cow mammary epithelial cells (DCMECs) from breast tissues and developed an in vitro model of lipopolysaccharide- (LPS-) induced inflammation to examine SIRT7 function and its potential role in inflammation. We showed that SIRT7 was significantly downregulated in LPS-treated DCMECs. SIRT7 knockdown significantly increased the LPS-stimulated production of inflammatory mediators, like reactive oxygen and nitric oxide, and upregulated TAB1 and TLR4. In addition, SIRT7 knockdown significantly increased the phosphorylation of TAK1 and NF-κBp65 in LPS-treated DCMECs. Moreover, SIRT7 knockdown promoted the translocation of NF-κBp-p65 to the cell nucleus and then increased the secretion of inflammatory cytokines (IL-1β and IL-6). In contrast, SIRT7 overexpression had the opposite effects when compared to SIRT7 knockdown in LPS-treated DCMECs. In addition, SIRT7 overexpression attenuated LPS-induced DCMEC apoptosis. Taken together, our results indicate that SIRT7 can suppress LPS-induced inflammation and apoptosis via the NF-κB signaling pathway. Therefore, SIRT7 may be considered as a potential pharmacological target for clinical mastitis therapy.

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Section: Discussionsupporting

confidence: 90%

SIRT7 Regulates Lipopolysaccharide-Induced Inflammatory Injury by Suppressing the NF-κB Signaling Pathway

Chen

et al. 2019

Oxidative Medicine and Cellular Longevity

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“…Consistent with our results, sirtuins, including SIRT7, have been reported to be key activators of antioxidant and redox signaling. 38,39 To the best of our knowledge, this is the first study illustrating that exosomal miR-17-5P restores ovarian function, rescues CTX-damaged hGCs and alleviates OS by inhibiting the expression of SIRT7 and its downstream target genes (PARP1, γH2AX and XRCC6) ( Figure 7). γH2AX, XRCC6, and PARP1 are critical mediators of DNA repair.…”

Section: Discussionmentioning

confidence: 93%

Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7

et al. 2020

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Premature ovarian insufficiency (POI) is clinically irreversible in women aged over 40 years. Although numerous studies have demonstrated satisfactory outcomes of mesenchymal stem cell therapy, the underlying therapeutic mechanism remains unclear. Exosomes were collected from the culture medium of human umbilical cord mesenchymal stem cells (hUMSCs) and assessed by electron microscopy and Western blot (WB) analysis. Then, exosomes were added to the culture medium of cyclophosphamide (CTX)‐damaged human granulosa cells (hGCs), and the mixture was injected into the ovaries of CTX‐induced POI model mice before detection of antiapoptotic and apoptotic gene expression. Next, the microRNA expression profiles of hUMSC‐derived exosomes (hUMSC‐Exos) were detected by small RNA sequencing. The ameliorative effect of exosomal microRNA‐17‐5P (miR‐17‐5P) was demonstrated by miR‐17‐5P knockdown before assessment of ovarian phenotype and function, reactive oxygen species (ROS) levels and SIRT7 expression. Finally, SIRT7 was inhibited or overexpressed by RNA interference or retrovirus transduction, and the protein expression of PARP1, γH2AX, and XRCC6 was analyzed. The ameliorative effect of hUMSC‐Exos on POI was validated. Our results illustrated that hUMSC‐Exos restored ovarian phenotype and function in a POI mouse model, promoted proliferation of CTX‐damaged hGCs and ovarian cells, and alleviated ROS accumulation by delivering exosomal miR‐17‐5P and inhibiting SIRT7 expression. Moreover, our findings elucidated that miR‐17‐5P repressed PARP1, γH2AX, and XRCC6 by inhibiting SIRT7. Our findings suggest a critical role for exosomal miR‐17‐5P and its downstream target mRNA SIRT7 in hUMSC transplantation therapy. This study indicates the promise of exosome‐based therapy for POI treatment.

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“…The related primers are listed in Table . Plasmid construction and mRNA synthesis were conducted as we reported previously (Gao et al, ). In brief, PCR products were cloned into the pCS2 + vector with Myc tags, and cRNAs were made using in vitro transcription with SP6 mMESSAGE mMACHINE (Ambion) according to the manufacturer's instruction.…”

Section: Methodsmentioning

confidence: 99%

Loss of HDAC3 contributes to meiotic defects in aged oocytes

Gao

et al. 2019

Aging Cell

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Maternal age-related decline in oocyte quality is associated with meiotic defects, but the underlying mechanisms remain to be explored. Histone deacetylase 3 (HDAC3) has been shown to govern multiple cellular events via deacetylating diverse substrates. We previously found that HDAC3 could promote meiotic apparatus assembly in mouse oocytes. In the present study, we identified a substantial reduction in HDAC3 protein in oocytes from old mice. Importantly, overexpression of HDAC3 in old oocytes not only partially prevents spindle/chromosome disorganization, but also significantly lowers the incidence of aneuploidy. Meanwhile, we noticed the elevated acetylation level of α-tubulin in oocytes derived from old mice. By employing sitedirected mutagenesis, we showed that acetylation-mimetic mutant tubulin-K40Q disrupts the kinetochore-microtubule attachments and results in the assembly failure of meiotic apparatus in mouse oocytes. Importantly, forced expression of tubulin-K40R (nonacetylatable-mimetic mutant) was capable of alleviating the defective phenotypes of oocytes from aged mice. To sum up, this study uncovers that loss of HDAC3 represents one potential mechanism mediating the effects of advanced maternal age on oocyte quality. K E Y W O R D Saneuploidy, HDACs, maternal aging, oocyte quality, reproduction

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SIRT7 functions in redox homeostasis and cytoskeletal organization during oocyte maturation

Cited by 32 publications

References 52 publications

SIRT7 Regulates Lipopolysaccharide-Induced Inflammatory Injury by Suppressing the NF-κB Signaling Pathway

SIRT7 Regulates Lipopolysaccharide-Induced Inflammatory Injury by Suppressing the NF-κB Signaling Pathway

Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7

Loss of HDAC3 contributes to meiotic defects in aged oocytes

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