Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 863, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2019.172695
Keywords
Pioglitazone; Autophagy; Tubular cells; Hypoxia/reoxygenation; AMP
Categories
Funding
- National Natural Science Foundation of China [81470929]
Ask authors/readers for more resources
Pioglitazone (Pio), a peroxisome proliferators-activated receptor-gamma (PPAR-gamma) agonist, may protect against renal ischemia/reperfusion injury (IRI). Recent studies have shown that autophagy plays a protective role in IRI. We aimed to evaluate whether autophagy was involved in pioglitazone-induced protection during tubular cell hypoxia/reoxygenation (H/R). Normal rat kidney proximal tubular cells NRK-52E were subjected to H/R injury, and they were divided into 6 groups: control, control + Pio, H/R, H/R + Pio, H/R + MA, H/R + MA + Pio. Autophagy-related proteins were primarily assessed by Western blot and TUNEL was performed to assess cell apoptosis. Our results showed pioglitazone pretreatment had a cytoprotective effect against H/R injury. The H/R + Pio group had an increased ratio of LC3-II to LC3-I and increased Beclin-1, decreased p62. Pioglitazone also reduced apoptosis and enhanced cell survival while inducing autophagy. Correspondingly, autophagy inhibition with 3-MA alleviated this protective effect. Furthermore, pioglitazone-induced enhancement of autophagy could be related to increased AMP-activated protein kinase (AMPK) phosphorylation and decreased Mammalian target of rapamycin (mTOR) phosphorylation. Thus, pioglitazone pretreatment protects against H/R injury by enhancting autophagy through the AMPK-mTOR signaling pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available