Heme oxygenase‑1 protects H2O2‑insulted glomerular mesangial cells from excessive autophagy.
Increasing evidence has demonstrated that the activation of heme oxygenase (HO)‑1 reduces autophagy stimulated by oxidative stress injury, in which the supraphysiological production of reactive oxygen species (ROS) is detected. However, the potential mechanism underlying this effect remains unclear. The present study aimed to investigate the function of HO‑1 activation in the regulation of autophagy in glomerular mesangial cells subjected to H2O2‑induced oxidative stress injury. The results demonstrated that the HO‑1 agonist, hemin, reduces the LC3 protein level, which was enhanced by H2O2 treatment. Furthermore, hemin‑activated HO‑1 may function as a regulator of oxidative stress‑induced autophagy in a dose‑dependent manner. Pharmacological activation of c‑Jun N‑terminal kinase (JNK) inhibited the effect of hemin, indicating that the JNK signaling pathway is associated with the mechanism of HO‑1 in impeding excessive autophagy. In addition to successfully alleviating H2O2‑induced oxidative stress and cellular apoptosis, hemin‑activated HO‑1 may provide cytoprotection against rapamycin, a specific autophagy agonist. The present result suggested the inhibitory action of HO‑1 in the avoidance of a potentially enhanced linkage between autophagy and apoptosis, particularly in the setting of excessive ROS. Therefore, enhancing the intracellular activity of HO‑1 may assist the crosstalk between oxidative stress, autophagy and apoptosis, and represent a novel therapeutic strategy for renal ischemic disease.
Department of Nephrology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Jia
J
Xu
Department of Cardiology, The Nangang Branch Hospital of Heilongjiang Provincial Hospital, Nangang, Heilongjiang 150000, P.R. China.
Jinshun
J
Li
Department of Pharmacy Intravenous Admixture Service, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 572000, P.R. China.
Jinhua
J
Wang
Department of Nephrology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Yanchun
Y
Chi
Department of Nephrology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Kun
K
Zhang
Department of Nephrology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Rui
R
Cui
D001343:Autophagy / Q000187:drug effects*; D002460:Cell Line; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000493:pharmacokinetics*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D050527:Mesangial Cells / Q000201:enzymology* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*
D006861:Hydrogen Peroxide; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D048670:MAP Kinase Kinase 4