Roles of heat shock protein A12A in the development of diabetic cardiomyopathy

Cell Stress Chaperones. 2024 Mar 12:S1355-8145(24)00055-5. doi: 10.1016/j.cstres.2024.03.004. Online ahead of print.ABSTRACTLong-term hyperglycemia can lead to diabetic cardiomyopathy (DCM), a main lethal complication of diabetes. However, the mechanisms underlying DCM development have not been fully elucidated. Heat shock protein A12A (HSPA12A) is the atypic member of HSP70 family. In the present study, we found that the expression of HSPA12A was upregulated in hearts of mice with streptozotocin (STZ)-induced diabetes, while ablation of HSPA12A improved cardiac systolic and diastolic dysfunction and increased cumulative survival of diabetic mice. An increased expression of HSPA12A was also found in H9c2 cardiac cells following treatment with high glucose (HG), while overexpression of HSPA12A enhanced the HG-induced cardiac cell death, as reflected by higher levels of propidium iodide (PI+) cells, lactate dehydrogenase (LDH) leakage, and caspase 3 cleavage. Moreover, the HG-induced increase of oxidative stress, as indicated by dihydroethidium (DHE) staining, was exaggerated by HSPA12A overexpression. Further studies demonstrated that the HG-induced increases of Akt and forkhead box transcription factors 1 (FOXO1) phosphorylation was diminished by HSPA12A overexpression, while pharmacologically inhibition of protein kinase B (Akt) further enhanced the HG-induced LDH leakage in HSPA12A overexpressed cardiac cells. Together, the results suggest that hyperglycemia upregulated HSP...
Source: Cell Stress and Chaperones - Category: Cytology Authors: Source Type: research