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Alpha-mangostin attenuates diabetic nephropathy in association with suppression of acid sphingomyelianse and endoplasmic reticulum stress

Author:
Liu, Tingting, Duan, Wang, Nizigiyimana, Paul, Gao, Lin, Liao, Zhouning, Xu, Boya, Liu, Lerong, Lei, Minxiang
Source:
Biochemical and biophysical research communications 2018 v.496 no.2 pp. 394-400
ISSN:
0006-291X
Subject:
albuminuria, animal disease models, apoptosis, blood glucose, diabetic nephropathy, diabetic neuropathy, endoplasmic reticulum stress, enzyme inhibitors, enzymes, kidneys, laboratory animals, protective effect, protein content, rats, transcription factors
Abstract:
Diabetic nephropathy is a common complication of diabetes, but there are currently few treatment options. The aim of this study was to gain insight into the effect of alpha-mangostin on diabetic nephropathy and possible related mechanisms.Goto-Kakizaki rats were used as a diabetic model and received alpha-mangostin or desipramine treatment with normal saline as a control. Ten age-matched Sprague Dawley rats were used as normal controls and treated with normal saline. At week 12, blood glucose, albuminuria, apoptosis and renal pathologic changes were assessed. Protein levels for acid sphingomyelinase, glucose-regulated protein 78, phosphorylated PKR-like ER-resident kinase, activated transcription factor 4, CCAAT/enhancer-binding protein, homologous protein), and cleaved-caspase12 were measured.The level of acid sphingomyelinase was significantly increased, and ER stress was activated in diabetic rat kidneys when compared to the control animals. When acid sphingomyelinase was inhibited by alpha-mangostin, the expression of ER stress-related proteins was down-regulated in association with decreased levels of diabetic kidney injury.Alpha-mangostin, an acid sphingomyelinase inhibitor plays a protective role in diabetic neuropathy by relieving ER stress induced-renal cell apoptosis.
Agid:
6280255