title: Inhibitory effects of cigarette smoke on glial inducible nitric oxide synthase and lack of protective properties against oxidative neurotoxins in vitro.
abstract: Epidemiological studies consistently report an inverse correlation between cigarette smoking and associated risk for Parkinson's disease (PD). The degeneration of dopaminergic neurons may involve the toxic metabolic products of glial cell monoamine oxidase (MAO) and inducible nitric oxide synthase (iNOS). This study evaluates the direct protective effects of cigarette smoke (CS) against potential neurotoxic products of MAO, such as 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA) and hydrogen peroxide (H2O2) in brain neuroblastoma. Moreover, the effects of CS were also evaluated on endotoxin/cytokine activated glioma iNOS protein expression and MAO enzyme activity. Cigarette smoke condensates (CSCs) were acquired from Marlboro 20 Class A and Kentucky 2R4F reference research (2R4F) cigarettes. The CSCs did not protect against 6-OHDA or H2O2 toxicity in neuroblastoma, and exhibited a very mild protective effect [approximately 10%] against MPP+. Neither CSC demonstrated antioxidant capability, but conversely contained high concentration of NO2-. Paradoxically, in glioma cells, iNOS protein expression and endogenous enzymatic NO2- production were significantly blocked by both CSCs. Both CSCs also inhibited glioma MAO-A and MAO-B [1.4.3.4]. Kinetic analysis indicated that 2R4F-CSC displayed competitive inhibition and the Marlboro-CSC exerted potent competitive and non-competitive inhibition. In conclusion, these data suggest that cigarette smoke does not appear to directly protect against the toxicity of the selected neurotoxins. In contrast, CS exerts pronounced effects on glia, whereby its presence can simultaneously attenuate cytokine induction of iNOS and MAO.
authors.affiliation: College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, Florida 32307, USA.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mazzio
authors.forename: Malak G
authors.initials: MG
authors.lastname: Kolta
authors.forename: R Renee
authors.initials: RR
authors.lastname: Reams
authors.forename: Karam F A
authors.initials: KF
authors.lastname: Soliman
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005910:Glioma / Q000473:pathology; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000633:toxicity; D008995:Monoamine Oxidase / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009457:Neuroglia / Q000187:drug effects / Q000201:enzymology*; D009498:Neurotoxins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D016877:Oxidants / Q000633:toxicity; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D011726:Pyridinium Compounds / Q000037:antagonists & inhibitors; D051381:Rats; D012906:Smoke / Q000009:adverse effects* / Q000032:analysis; D012907:Smoking / Q000503:physiopathology*; D013565:Sympatholytics / Q000037:antagonists & inhibitors / Q000633:toxicity
chemical_list: D009498:Neurotoxins; D009573:Nitrites; D016877:Oxidants; D011726:Pyridinium Compounds; D012906:Smoke; D013565:Sympatholytics; D009569:Nitric Oxide; C026560:1-(4-methoxyphenyl)pyridinium; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D008995:Monoamine Oxidase