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The PKCβ-p66shc-NADPH oxidase pathway plays a crucial role in diabetic nephropathy
- Source :
- Journal of Pharmacy and Pharmacology. 71:338-347
- Publication Year :
- 2018
- Publisher :
- Oxford University Press (OUP), 2018.
-
Abstract
- Objectives Oxidative stress plays a critical role in the pathogenesis of diabetic nephropathy (DN). p66shc is closely related to oxidative stress. However, the exact mechanism of its involvement in diabetic nephropathy is poorly understood. This study aimed to investigate the role of the p66shc-related pathway in diabetic nephropathy. Methods In an in-vivo experiment, rats were injected with streptozotocin to induce early diabetic nephropathy. The treatment groups were an aminoguanidine group and an enzastaurin group. In an in-vitro experiment, human renal proximal tubule epithelial cells (HK-2 cells) were cultured and incubated with high glucose. Key findings Upregulated protein expression of p66shc and p-p66shc was found in vivo and in vitro when cells were stimulated by high levels of glucose; this effect was accompanied by enhanced oxidative stress and damaged renal function, both of which were alleviated by p66shc siRNA. p66shc regulated NADPH oxidase, further promoting activation of oxidative stress. As an inhibitor of PKCβ, enzastaurin reduced the abnormal expression of p66shc and NADPH oxidase and alleviated renal injury. Conclusions This study demonstrated enzastaurin alleviated diabetic renal injury via modulation of the PKCβ-p66shc-NADPH oxidase pathway, which provided a new perspective for the treatment of early DN.
- Subjects :
- Male
Indoles
Src Homology 2 Domain-Containing, Transforming Protein 1
Pharmaceutical Science
Pharmacology
Kidney
medicine.disease_cause
030226 pharmacology & pharmacy
Rats, Sprague-Dawley
Diabetic nephropathy
Pathogenesis
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Enzastaurin
Downregulation and upregulation
Protein Kinase C beta
medicine
Animals
Humans
Diabetic Nephropathies
RNA, Small Interfering
Cells, Cultured
Oxidase test
NADPH oxidase
biology
business.industry
NADPH Oxidases
Epithelial Cells
medicine.disease
Streptozotocin
Rats
Up-Regulation
Oxidative Stress
Glucose
chemistry
030220 oncology & carcinogenesis
biology.protein
Reactive Oxygen Species
business
Oxidation-Reduction
Oxidative stress
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 20427158 and 00223573
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmacy and Pharmacology
- Accession number :
- edsair.doi.dedup.....ccabb0d471f5c91a243bd952d37ef6a5