1. Valproate attenuates diabetic nephropathy through inhibition of endoplasmic reticulum stress-induced apoptosis
- Author
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Lian‑Kun Sun, Xin‑Yi Sun, Xiao‑Chun Yang, Han‑Jiao Qin, Dong‑Ming Zhao, Ze Zhang, Xiao‑Ning Li, and Ye Xu
- Subjects
Male ,0301 basic medicine ,Cancer Research ,medicine.drug_class ,CHOP ,Kidney ,Biochemistry ,Histones ,Histone H4 ,03 medical and health sciences ,Genetics ,medicine ,Animals ,Diabetic Nephropathies ,Rats, Wistar ,Promoter Regions, Genetic ,Endoplasmic Reticulum Chaperone BiP ,Molecular Biology ,Heat-Shock Proteins ,Transcription Factor CHOP ,biology ,Valproic Acid ,diabetic nephropathy ,Endoplasmic reticulum ,Histone deacetylase inhibitor ,histone acetylation ,apoptosis ,Acetylation ,Articles ,Endoplasmic Reticulum Stress ,Mitochondria ,Disease Models, Animal ,030104 developmental biology ,Histone ,medicine.anatomical_structure ,Oncology ,valproate ,biology.protein ,Cancer research ,Molecular Medicine ,lipids (amino acids, peptides, and proteins) - Abstract
Previous studies have suggested that endoplasmic reticulum stress (ERS) is one of the mechanisms responsible for the pathogenesis of diabetic nephropathy (DN). Histone acetylation modification can regulate the transcription of genes and is involved in the regulation of ERS. Valproate (VPA), a nonselective histone deacetylase inhibitor, has been reported to have a protective role in kidney tissue injury, however, whether VPA can prevent DN remains to be elucidated. In the present study, it was found that VPA increases the expression of glucose-regulated protein (GRP78) and reduces the protein expression of C/EBP-homologous protein (CHOP), growth arrest and DNA-damage-inducible gene 153 and caspase-12 in a rat model of DN. VPA can reduce renal cell apoptosis and alleviate proteinuria and alterations in serum creatinine. VPA also upregulates the acetylation level of histone H4 in the promoter of GRP78 and downregulates the acetylation level of histone H4 in the promoter of CHOP. Collectively, the data indicate that VPA can relieve ERS and reduce renal cell apoptosis, and thus attenuate renal injury in a rat model of DN by regulating the acetylation level of histone H4 in ERS-associated protein promoters. more...
- Published
- 2015
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