Lumbrokinase Attenuates Side-Stream-Smoke-Induced Apoptosis and Autophagy in Young Hamster Hippocampus: Correlated with eNOS Induction and NF魏B/iNOS/COX-2 Signaling Suppression

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• 作者：Chih-Yang Huang ; Wei-Wen Kuo ; Hung-En Liao ; Yueh-Min Lin ; Chia-Hua Kuo ; Fuu-Jen Tsai ; Chang-Hai Tsai ; Jia-Long Chen ; Jing-Ying Lin
• 刊名：Chemical Research in Toxicology
• 出版年：2013
• 出版时间：May 20, 2013
• 年：2013
• 卷：26
• 期：5
• 页码：654-661
• 全文大小：339K
• 年卷期：v.26,no.5(May 20, 2013)
• ISSN：1520-5010

文摘

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 NF魏B/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.