Exogenous H(2)S facilitating ubiquitin aggregates clearance via autophagy attenuates type 2 diabetes-induced cardiomyopathy.
Exogenous H(2)S facilitating ubiquitin aggregates clearance via autophagy attenuates type 2 diabetes-induced cardiomyopathy.
复制标题
外源性 H2S 通过自噬促进泛素聚集体清除，减轻 2 型糖尿病引起的心肌病
DOI：
10.1038/cddis.2017.380
复制
发表时间：
2017-08-10
影响因子：
9
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Wu J;Tian Z;Sun Y;Lu C;Liu N;Gao Z;Zhang L;Dong S;Yang F;Zhong X;Xu C;Lu F;Zhang W
糖尿病心肌病（DCM）是糖尿病的严重并发症。硫化氢（H2S）是一种新发现的气态信号分子，在许多调节功能中发挥着重要作用。本研究旨在探讨外源性H2S对2型糖尿病（T2 DCM）心肌细胞自噬的影响及其可能机制。本研究发现，硫氢化钠（NaHS）可减轻db/db小鼠左室重量的增加，增加左室容积，减少活性氧（ROS）的产生，减少H2S的产生。NaHS促进自噬体内容物降解，降低P62（自噬的已知底物）的表达，并增加微管相关蛋白1轻链3 II的表达。它还增加了db/db小鼠心脏中自噬相关蛋白7（ATG 7）和Beclin 1的表达。NaHS增加db/db小鼠心脏Kelch样ECH相关蛋白1（Keap-1）的表达，降低泛素化水平。二硫键抑制剂1，4-二硫苏糖醇（1，4-Dithiothreitol，Dithiothreitol）可增加高糖和棕榈酸处理的H9 C2细胞中Keap-1的泛素化水平，抑制Keap-1的表达，并消除NaHS对H9 C2细胞中泛素聚集体清除和ROS产生的影响。总之，外源性H2S通过自噬促进泛素聚集体的清除，这可能在db/db小鼠心肌中发挥其抗氧化作用。此外，外源性H2S通过抑制Keap-1的泛素化而增加其表达，这可能在自噬清除泛素聚集体中起重要作用。我们的研究结果提供了新的见解的机制负责的抗氧化作用的H2 S的背景下T2 DCM。
Diabetic cardiomyopathy (DCM) is a serious complication of diabetes. Hydrogen sulphide (H 2 S), a newly found gaseous signalling molecule, has an important role in many regulatory functions. The purpose of this study is to investigate the effects of exogenous H 2 S on autophagy and its possible mechanism in DCM induced by type II diabetes (T2DCM). In this study, we found that sodium hydrosulphide (NaHS) attenuated the augment in left ventricular (LV) mass and increased LV volume, decreased reactive oxygen species (ROS) production and ameliorated H 2 S production in the hearts of db/db mice. NaHS facilitated autophagosome content degradation, reduced the expression of P62 (a known substrate of autophagy) and increased the expression of microtubule-associated protein 1 light chain 3 II. It also increased the expression of autophagy-related protein 7 (ATG7) and Beclin1 in db/db mouse hearts. NaHS increased the expression of Kelch-like ECH-associated protein 1 (Keap-1) and reduced the ubiquitylation level in the hearts of db/db mice. 1, 4-Dithiothreitol, an inhibitor of disulphide bonds, increased the ubiquitylation level of Keap-1, suppressed the expression of Keap-1 and abolished the effects of NaHS on ubiquitin aggregate clearance and ROS production in H9C2 cells treated with high glucose and palmitate. Overall, we concluded that exogenous H 2 S promoted ubiquitin aggregate clearance via autophagy, which might exert its antioxidative effect in db/db mouse myocardia. Moreover, exogenous H 2 S increased Keap-1 expression by suppressing its ubiquitylation, which might have an important role in ubiquitin aggregate clearance via autophagy. Our findings provide new insight into the mechanisms responsible for the antioxidative effects of H 2 S in the context of T2DCM.
登录
查看更多内容
影响因子：
5.1
作者：
Nakka, Venkata Prasuja;Prakash-babu, Phanithi;Vemuganti, Raghu
通讯作者：
Vemuganti, Raghu
影响因子：
20.1
作者：
Calvert JW;Jha S;Gundewar S;Elrod JW;Ramachandran A;Pattillo CB;Kevil CG;Lefer DJ
通讯作者：
Lefer DJ
DOI：
10.1124/jpet.105.092023
发表时间：
2006-02-01
影响因子：
3.5
作者：
Bian, JS;Yong, QC;Moore, PK
通讯作者：
Moore, PK
DOI：
10.1016/j.bbadis.2012.07.015
发表时间：
2012-11-01
影响因子：
6.2
作者：
Cecarini, Valentina;Bonfili, Laura;Eleuteri, Anna Maria
通讯作者：
Eleuteri, Anna Maria
影响因子：
6.6
作者：
Hourihan, John M.;Kenna, J. Gerry;Hayes, John D.
通讯作者：
Hayes, John D.