Sentrin-specific protease 3（SENP3）, a member of the desumoylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, its implication in myocardial ischemia re...Sentrin-specific protease 3（SENP3）, a member of the desumoylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, its implication in myocardial ischemia reperfusion（MIR） injury is unclear. Here, we observed that SENP3 was expressed and upregulated in the mouse heart depending on reactive oxygen species（ROS） production in response to MIR injury. By utilizing si RNA-mediated cardiac specific gene silencing, SENP3 knockdown was demonstrated to significantly reduce MIR-induced infarct size and improve cardiac function. Mechanistic studies indicated that SENP3 silencing ameliorated myocardial apoptosis mainly via suppression of endoplasmic reticulum（ER） stress and mitochondrial-mediated apoptosis pathways. By contrast, adenovirusmediated cardiac SENP3 overexpression significantly exaggerated MIR injury. Further molecular analysis revealed that SENP3 promoted mitochondrial translocation of dynamin-related protein 1（Drp1） in reperfused myocardium. In addition, mitochondrial division inhibitor-1（Mdivi-1）, a pharmacological inhibitor of Drp1, significantly attenuated the exaggerated mitochondrial abnormality and cardiac injury by SENP3 overexpression after MIR injury. Taken together, we provide the first direct evidence that SENP3 upregulation pivotally contributes to MIR injury in a Drp1-dependent manner, and suggest that SENP3 suppression may hold therapeutic promise for constraining MIR injury.展开更多
Objective This study elucidated the function and role of SUMOylation in type Ⅰ endometrial carcinoma.Methods Fifty type Ⅰ endometrial carcinoma cases and para-cancer tissue samples were collected.The expression leve...Objective This study elucidated the function and role of SUMOylation in type Ⅰ endometrial carcinoma.Methods Fifty type Ⅰ endometrial carcinoma cases and para-cancer tissue samples were collected.The expression levels of ubiquitin-conjugating enzyme E2I(Ube2 i,Ubc9) and small ubiquitin-like modifier 1(SUMO1)/sentrin-specific peptidase 1(SENP1) proteins were examined using immunohistochemistry and the correlation with clinicopathological parameters was analyzed.Results Ubc9 expression in type Ⅰ endometrial carcinoma tissues was significantly higher than that in the para-cancer tissues;in contrast,the expression of the SENP1 protein was markedly lower than that in the para-cancer tissues.Ubc9 and SENP1 expression levels were negatively correlated and were associated with tumor differentiation,but not age,depth of invasion,tumor stage,and lymph node metastasis.Conclusion SUMOylation modification plays a major role in the pathogenesis and development of type Ⅰ endometrial carcinoma.Thus,it could be a potential target for the treatment of endometrial cancer.展开更多
基金supported by the National Science Fund for Distinguished Young Scholars(No.81625002)the National Natural Science Foundation of China(Nos.81470389,81270282,81330006,81500200,81500221,81070176,81170192,81400261,81600268,and 81601238)+5 种基金the Program of Shanghai Academic Research Leader(18XD1402400)the Shanghai Municipal Education Commission Gaofeng Clinical Medicine Grant Support(No.20152209)Shanghai Shenkang Hospital Development Center(16CR3034A)Shanghai Jiao Tong University(YG2013MS42 and YG2015MS54)Shanghai Jiao Tong University School of Medicine(15ZH1003 and 14XJ10019)the Shanghai Sailing Program(18YF1413000)
文摘Sentrin-specific protease 3（SENP3）, a member of the desumoylating enzyme family, is known as a redox sensor and could regulate multiple cellular signaling pathways. However, its implication in myocardial ischemia reperfusion（MIR） injury is unclear. Here, we observed that SENP3 was expressed and upregulated in the mouse heart depending on reactive oxygen species（ROS） production in response to MIR injury. By utilizing si RNA-mediated cardiac specific gene silencing, SENP3 knockdown was demonstrated to significantly reduce MIR-induced infarct size and improve cardiac function. Mechanistic studies indicated that SENP3 silencing ameliorated myocardial apoptosis mainly via suppression of endoplasmic reticulum（ER） stress and mitochondrial-mediated apoptosis pathways. By contrast, adenovirusmediated cardiac SENP3 overexpression significantly exaggerated MIR injury. Further molecular analysis revealed that SENP3 promoted mitochondrial translocation of dynamin-related protein 1（Drp1） in reperfused myocardium. In addition, mitochondrial division inhibitor-1（Mdivi-1）, a pharmacological inhibitor of Drp1, significantly attenuated the exaggerated mitochondrial abnormality and cardiac injury by SENP3 overexpression after MIR injury. Taken together, we provide the first direct evidence that SENP3 upregulation pivotally contributes to MIR injury in a Drp1-dependent manner, and suggest that SENP3 suppression may hold therapeutic promise for constraining MIR injury.
文摘Objective This study elucidated the function and role of SUMOylation in type Ⅰ endometrial carcinoma.Methods Fifty type Ⅰ endometrial carcinoma cases and para-cancer tissue samples were collected.The expression levels of ubiquitin-conjugating enzyme E2I(Ube2 i,Ubc9) and small ubiquitin-like modifier 1(SUMO1)/sentrin-specific peptidase 1(SENP1) proteins were examined using immunohistochemistry and the correlation with clinicopathological parameters was analyzed.Results Ubc9 expression in type Ⅰ endometrial carcinoma tissues was significantly higher than that in the para-cancer tissues;in contrast,the expression of the SENP1 protein was markedly lower than that in the para-cancer tissues.Ubc9 and SENP1 expression levels were negatively correlated and were associated with tumor differentiation,but not age,depth of invasion,tumor stage,and lymph node metastasis.Conclusion SUMOylation modification plays a major role in the pathogenesis and development of type Ⅰ endometrial carcinoma.Thus,it could be a potential target for the treatment of endometrial cancer.
