Role of oxidative stress and heme oxygenase activity in morphine-induced glomerular epithelial cell growth.
Opiate addiction has been reported to contribute to the progression of renal injury. In addition, opiate addiction is a major risk factor for the development of human immunodeficiency virus-associated nephropathy. In the present study, we evaluated the effects of morphine, an active metabolite of heroin, on glomerular epithelial cell (GEC) growth and the involved molecular mechanism. At lower concentrations, morphine promoted GEC proliferation; however, at higher concentrations, morphine triggered apoptosis. Antioxidants inhibited morphine-induced proliferation as well as apoptosis. Similarly, free radical scavengers prevented morphine-induced GEC proliferation and apoptosis. Because proliferative and proapoptotic effects of morphine were inhibited by free radical scavengers as well as antioxidants, it appears that these effects of morphine are mediated through oxidative stress. Hemin, an inducer of heme oxygenase (HO) activity, inhibited GEC proliferation and promoted GEC apoptosis under basal and morphine-stimulated conditions. On the other hand, zinc protoporphyrin, an inhibitor of HO activity, promoted GEC proliferation and inhibited GEC apoptosis under basal as well as morphine-stimulated conditions. These findings suggest that HO activity is directly related to GEC apoptosis and inversely related to GEC proliferation. Morphine, de novo, had bimodal effects on HO activity: lower concentrations increased and higher concentrations decreased HO activity. It appears that HO activity may be modifying morphine-induced GEC growth.
Patel
Jaimita
J
Immunology and Inflammation Center for Excellence, North Shore-Long Island Jewish Research Institute, New Hyde Park, NY 11040, USA.
Manjappa
Nagarathna
N
Bhat
Rajani
R
Mehrotra
Pavni
P
Bhaskaran
Madhu
M
Singhal
Pravin C
PC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology* / Q000502:physiology; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats
D009294:Narcotics; D009020:Morphine; D006419:Heme Oxygenase (Decyclizing)