title: Nerve growth factor induces anti-apoptotic heme oxygenase-1 in rat pheochromocytoma PC12 cells.
abstract: Nerve growth factor (NGF) and heme oxygenases (HOs) both exert neuroprotective effects. To characterize the role of HOs in the prevention of apoptosis by NGF, we investigated the effect of NGF on the expression of HOs in serum-deprived PC12 cells. Serum deprivation (SD) led to a rapid decrease in HO-1 gene expression followed by induction of apoptosis. Incubation of serum-deprived PC12 cells with NGF prevented apoptosis and increased HO-1 mRNA and protein levels, as well as HO enzyme activity. HO-2 gene expression was unaffected by SD or NGF. Incubation of cells with mitogen-activated protein kinase kinase (MEK) inhibitors (PD98059 or U0126) attenuated the ability of NGF to increase HO-1 expression and to protect PC12 cells against SD-induced apoptosis. NGF augmented HO-1 gene transcription but did not alter HO-1 mRNA stability. HO inhibitors or antisense HO-1 RNA decreased the ability of NGF to prevent cell apoptosis. Inhibition of HO activity enhanced intracellular reactive oxygen species (ROS) production and attenuated NGF-induced reduction of ROS in serum-deprived PC12 cells. These results demonstrate that NGF enhances HO-1 gene transcription via MEK activation and that the induction of HO-1 plays an important role in the antioxidative and antiapoptotic effects of NGF in serum-deprived PC12 cells.
authors.affiliation: Cardiovascular Research Center of the Department of Medicine, Harvard Medical School, Charlestown, Massachusetts, USA. Liu@CVRC.MGH.HARVARD.EDU
authors.forename: Heling
authors.initials: H
authors.lastname: Liu
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nowak
authors.forename: Wei
authors.initials: W
authors.lastname: Chao
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Bloch
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D051547:Heme Oxygenase-1; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D010673:Pheochromocytoma / Q000188:drug therapy / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D020929:Mitogen-Activated Protein Kinase Kinases