Heme oxygenase-1 protects [H.sub.2][O.sub.2]-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 [H.SUB.2][O.SUB.2]-induced oxidative stress injury. The results demonstrated that the HO-1 agonist, hemin, reduces the LC3 protein level, which was enhanced by [H.SUB.2][O.SUB.2] 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 [H.SUB.2][O.SUB.2]-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. Key words: heme oxygenase-1, oxidative stress, autophagy, apoptosis, glomerular mesangial cell