Exogenous H2S prevents the nuclear translocation of PDC‐E1 and inhibits vascular smooth muscle cell proliferation in the diabetic state
| Autor: | jingyuan Tang, Ning Liu, Linxue Zhang, lingxue Chen, Fanghao Lu, jiaxin Kang, Shiyun Dong, xiaoshu Jiang, mingyu Li, Weihua Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Vascular smooth muscle
Cell Myocytes Smooth Muscle Cell Culture Techniques pyruvate dehydrogenase complex‐E1 (PDC‐E1) Chromosomal translocation macromolecular substances Mitochondrion hydrogen sulphide (H2S) Muscle Smooth Vascular Mitochondrial Proteins Mice Cyclin D1 medicine Animals Pyruvate Dehydrogenase (Lipoamide) Hydrogen Sulfide Cell Proliferation Cell Nucleus biology Cell growth Chemistry hemic and immune systems Cell Biology Original Articles Pyruvate dehydrogenase complex equipment and supplies Cell biology Proliferating cell nuclear antigen Mitochondria Mice Inbred C57BL medicine.anatomical_structure diabetes mellitus biology.protein Molecular Medicine Original Article vascular smooth muscle cell |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | Hydrogen sulphide (H2S) inhibits vascular smooth muscle cell (VSMC) proliferation induced by hyperglycaemia and hyperlipidaemia; however, the mechanisms are unclear. Here, we observed lower H2S levels and higher expression of the proliferation‐related proteins PCNA and cyclin D1 in db/db mouse aortae and vascular smooth muscle cells treated with 40 mmol/L glucose and 500 μmol/L palmitate, whereas exogenous H2S decreased PCNA and cyclin D1 expression. The nuclear translocation of mitochondrial pyruvate dehydrogenase complex‐E1 (PDC‐E1) was significantly increased in VSMCs treated with high glucose and palmitate, and it increased the level of acetyl‐CoA and histone acetylation (H3K9Ac). Exogenous H2S inhibited PDC‐E1 translocation from the mitochondria to the nucleus because PDC‐E1 was modified by S‐sulfhydration. In addition, PDC‐E1 was mutated at Cys101. Overexpression of PDC‐E1 mutated at Cys101 increased histone acetylation (H3K9Ac) and VSMC proliferation. Based on these findings, H2S regulated PDC‐E1 S‐sulfhydration at Cys101 to prevent its translocation from the mitochondria to the nucleus and to inhibit VSMC proliferation under diabetic conditions. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text