Probucol inhibits JAK2−STAT pathway activation and protects human glomerular mesangial cells from tert-butyl hydroperoxide induced premature senescence
| Autor: | Hongli Zhou, Yarong Han, Bo Huang, Ruixia Jin, Shuo Chen |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
STAT3 Transcription Factor
Senescence Cell Survival Physiology Glomerular Mesangial Cell Probucol tert-Butylhydroperoxide Physiology (medical) medicine Humans Phosphorylation STAT3 Protein Kinase Inhibitors Cells Cultured Cellular Senescence Cell Proliferation bcl-2-Associated X Protein Pharmacology biology Cell growth JAK-STAT signaling pathway Cell Cycle Checkpoints General Medicine Janus Kinase 2 beta-Galactosidase Cell biology STAT Transcription Factors STAT1 Transcription Factor Proto-Oncogene Proteins c-bcl-2 Biochemistry Apoptosis Mesangial Cells biology.protein Kidney disorder Signal Transduction medicine.drug |
| Zdroj: | Canadian Journal of Physiology and Pharmacology. 91:671-679 |
| ISSN: | 1205-7541 0008-4212 |
| DOI: | 10.1139/cjpp-2012-0343 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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