Hydrogen sulphide reduced the accumulation of lipid droplets in cardiac tissues of db/db mice via Hrd1 S-sulfhydration.
Hydrogen sulphide reduced the accumulation of lipid droplets in cardiac tissues of db/db mice via Hrd1 S-sulfhydration.
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DOI：
10.1111/jcmm.16781
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发表时间：
2021-10
影响因子：
5.3
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Sun Y;Zhang L;Lu B;Wen J;Wang M;Zhang S;Li Q;Shu F;Lu F;Liu N;Peng S;Zhao Y;Dong S;Lu F;Zhang W;Wang Y
脂滴积聚（LDs）诱导2型糖尿病患者心功能障碍。最近的研究表明，硫化氢（H2S）可以改善db/db小鼠的心功能，但其对心脏组织ld形成的调节作用尚不清楚。给Db/ Db小鼠注射40 μmol·kg‐1的NaHS，持续12周。H9c2细胞分别用高糖（40 mmol/L）、油酸（200µmol/L）、棕榈酸（200µmol/L）和NaHS（100µmol/L）处理48小时。构建了过表达野生型Hrd1和Cys115突变Hrd1的质粒。测定了Hrd1与DGAT1和DGAT2的相互作用、DGAT1和DGAT2的泛素化水平以及Hrd1的S -巯基化反应。外源性H2S可改善db/db小鼠的心功能，降低内质网应激，减少ld数量。外源H2S可提高db/db小鼠心脏组织中DGAT 1和DGAT 2的泛素化水平，增加Hrd1的表达。NaHS对Hrd1的S -磺化作用增强了Hrd1与DGAT1和dgat2的相互作用，从而抑制LD的形成。我们的研究结果表明H2S修饰Hrd1在Cys115处的S -磺化作用减少了db/db小鼠心脏组织LD的积累。
Accumulation of lipid droplets (LDs) induces cardiac dysfunctions in type 2 diabetes patients. Recent studies have shown that hydrogen sulphide (H2S) ameliorates cardiac functions in db/db mice, but its regulation on the formation of LDs in cardiac tissues is unclear. Db/db mice were injected with NaHS (40 μmol·kg‐1) for twelve weeks. H9c2 cells were treated with high glucose (40 mmol/L), oleate (200 µmol/L), palmitate (200 µmol/L) and NaHS (100 µmol/L) for 48 hours. Plasmids for the overexpression of wild‐type Hrd1 and Hrd1 mutated at Cys115 were constructed. The interaction between Hrd1 and DGAT1 and DGAT2, the ubiquitylation level of DGAT1 and 2, the S‐sulfhydration of Hrd1 were measured. Exogenous H2S ameliorated the cardiac functions, decreased ER stress and reduced the number of LDs in db/db mice. Exogenous H2S could elevate the ubiquitination level of DGAT 1 and 2 and increased the expression of Hrd1 in cardiac tissues of db/db mice. The S‐sulfhydration of Hrd1 by NaHS enhanced the interaction between Hrd1 and DGAT1 and 2 to inhibit the formation of LD. Our findings suggested that H2S modified Hrd1 S‐sulfhydration at Cys115 to reduce the accumulation of LDs in cardiac tissues of db/db mice.
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