Maternal nicotine exposure increases oxidative stress in the offspring
Maternal nicotine exposure increases oxidative stress in the offspring
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DOI：
10.1016/j.freeradbiomed.2008.02.010
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发表时间：
2008-06-01
影响因子：
7.4
通讯作者：
Holloway, Alison C.
中科院分区：
文献类型：
--
作者：
Bruin, Jennifer E.;Petre, Maria A.;Holloway, Alison C.
胎儿和新生儿尼古丁暴露导致β细胞凋亡和β细胞质量损失，但其潜在机制尚不清楚。本研究的目的是确定母体来源的尼古丁是否可以在胎儿和新生儿发育过程中通过胰腺烟碱乙酰胆碱受体（nAChR）诱导胰腺氧化应激。雌性Wistar大鼠在交配前通过皮下注射给予生理盐水或尼古丁（1 mg/kg/天）2周，直至断奶（出生后第21天）。在雄性后代中，nAChR亚基mRNA表达的特点是在发育中的胰腺和各种氧化应激标记物进行了测量，在断奶后的盐水和尼古丁暴露。nAChR亚基α 2-α 4、α 6、α 7和β 2-β 4在发育期间存在于胰腺中。胎儿和新生儿暴露于尼古丁显着增加胰腺GPx-1和MnSOD蛋白的表达，以及胰岛ROS的生产。此外，尼古丁暴露的后代蛋白质羰基形成较高，相对于对照组，特别是在线粒体部分。血清8-isoPG水平也呈非显著性升高趋势。这些数据表明，胎儿和新生儿胰腺中的p细胞凋亡可能是尼古丁通过其受体直接作用的结果，并且这种作用可能通过增加氧化应激介导。(C)2008年爱思唯尔公司All rights reserved.
Fetal and neonatal nicotine exposure causes beta-cell apoptosis and loss of beta-cell mass, but the underlying mechanisms are unknown. The goal of this study was to determine whether maternally derived nicotine can act via the pancreatic nicotinic acetylcholine receptor (nAChR) during fetal and neonatal development to induce oxidative stress in the pancreas. Female Wistar rats were given saline or nicotine (1 mg/kg/day) via subcutaneous injection for 2 weeks prior to mating until weaning (postnatal day 21). In male offspring, nAChR subunit mRNA expression was characterized in the developing pancreas and various oxidative stress markers were measured at weaning following saline and nicotine exposure. The nAChR subunits alpha 2-alpha 4, alpha 6, alpha 7, and beta 2-beta 4 were present in the pancreas during development. Fetal and neonatal exposure to nicotine significantly increased pancreatic GPx-1 and MnSOD protein expression, as well as islet ROS production. Furthermore, protein carbonyl formation was higher in nicotine-exposed offspring relative to controls, particularly within the mitochondrial fraction. There was also a nonsignificant trend toward higher serum 8-isoPG levels. These data suggest that p-cell apoptosis in the fetal and neonatal pancreas may be the result of a direct effect of nicotine via its receptor and that this effect may be mediated through increased oxidative stress. (C) 2008 Elsevier Inc. All rights reserved.