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- Title
Probucol inhibits JAK2−STAT pathway activation and protects human glomerular mesangial cells from tert-butyl hydroperoxide induced premature senescence.
- Authors
Zhou, Hongli; Huang, Bo; Han, Yarong; Jin, Ruixia; Chen, Shuo
- Abstract
Human mesangial cells (HMCs) have a finite lifespan and eventually enter irreversible growth arrest known as cellular senescence, which is thought to contribute to kidney ageing and age-related kidney disorders such as chronic kidney disease. The JAK2−STAT pathway plays a pivotal role in transmitting cytokine signals, including cell proliferation, apoptosis, and differentiation, but whether it could regulate HMC senescence still remains to be explored. In our study, tert-butyl hydroperoxide (tBHP)-induced cells accelerated HMC senescence, as judged by increased senescence-associated β-galactosidase stained positive cells, morphological changes, and G0−G1 cell cycle arrest. STAT1 and STAT3 activity were increased in tBHP-induced cells. After tBHP treatment, Bcl-2 protein expression decreased and Bax protein expression increased. Blocking the JAK2−STAT pathway with AG490 and using probucol significantly inhibited the progression of HMC senescence. Bax protein expression decreased, but Bcl-2 protein expression increased after AG490 and probucol treatment. Our results indicated that the JAK2−STAT pathway might mediate tBHP-induced HMC senescence through the Bcl-2−Bax pathway, and that probucol could attenuate HMC senescence by regulating STATs.
- Subjects
PROBUCOL; STAT proteins; GLOMERULAR filtration rate; HYDROPEROXIDES; KIDNEY disease treatments; CELLULAR aging; KIDNEY aging
- Publication
Canadian Journal of Physiology & Pharmacology, 2013, Vol 91, Issue 9, p671
- ISSN
0008-4212
- Publication type
Article
- DOI
10.1139/cjpp-2012-0343