title: Lumbrokinase attenuates side-stream-smoke-induced apoptosis and autophagy in young hamster hippocampus: correlated with eNOS induction and NFκB/iNOS/COX-2 signaling suppression.
abstract: Recent studies have found that cigarette smoke is epidemiologically linked to an increased risk for impaired cognitive development in adolescents. This study evaluated the influence of side stream smoke (SSS) exposure on hippocampal apoptosis and of the lumbrokinase (LK) effects on SSS induced apoptosis in young hamster hippocampus. Twenty male hamsters at six weeks of age were randomly divided into control group, SSS group (exposed to tobacco cigarettes smoke at doses of 10 cigarettes for 30 min twice a day for 1 month), and SSS hamsters with LK treatment (1.2 mg/kg, ip) for twice a week for 1 month. TUNEL assay and Western blotting were performed. The TUNEL-positive apoptotic cells, as well as Fas-dependent activity and mitochondria-dependent apoptotic pathways, such as Fas, FADD, activated caspase-8, t-Bid, activated caspase-9, and activated caspase-3, were significantly increased in the SSS-exposed hippocampus compared to the control and highly attenuated in the LK treatment group. Additionally, SSS exposure significantly increased the autophagy marker proteins, Beclin-1, ATG7, and LC3-II levels, in the hippocampus compared to those in the control group and obviously attenuated after LK treatment. LK also reduced hippocampus injury by enhancing eNOS expression and remarkably inhibited the proinflammatory NFκB/iNOS/COX-2 signaling activity. We found that the detrimental effects of SSS on the hippocampus are truly mediated by cell apoptosis and autophagy. However, LK reduced the hippocampus apoptosis and autophagy related injuries induced by SSS in a widespread manner. We suggest that LK presents protective effects on hippocampus apoptosis and has therapeutic potential against abnormal hippocampal function.
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, 2. Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: Hung-En
authors.initials: HE
authors.lastname: Liao
authors.forename: Yueh-Min
authors.initials: YM
authors.lastname: Lin
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chang-Hai
authors.initials: CH
authors.lastname: Tsai
authors.forename: Jia-Long
authors.initials: JL
authors.lastname: Chen
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D006224:Cricetinae; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D010450:Endopeptidases / Q000378:metabolism*; D004790:Enzyme Induction / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012906:Smoke / Q000009:adverse effects*; D013329:Structure-Activity Relationship; D062789:Tobacco Products
chemical_list: D016328:NF-kappa B; D012906:Smoke; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051546:Cyclooxygenase 2; D010450:Endopeptidases; C083421:lumbrokinase