Chronic nicotine exposure exacerbates acute renal ischemic injury
Chronic nicotine exposure exacerbates acute renal ischemic injury
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DOI：
10.1152/ajprenal.00041.2011
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发表时间：
2011-07-01
影响因子：
4.2
通讯作者：
Juncos, Luis A.
中科院分区：
文献类型：
--
作者：
Arany, Istvan;Grifoni, Samira;Juncos, Luis A.
Arany I，Grifoni S，Clark JS，Csongradi E，Maric C，容科斯LA.慢性尼古丁暴露加重急性肾缺血性损伤。美国肾脏生理学杂志301：F125-F133，2011年。首次发表于2011年4月20日; doi：10.1152/ajprenal.00041.2011。最近的流行病学报告表明，吸烟对肾功能有负面影响，不仅在肾病患者中，而且可能在健康人群中增加肾脏风险。研究表明，尼古丁，一种主要的烟草生物碱，将吸烟与肾功能障碍联系起来。虽然一些研究表明，吸烟/慢性尼古丁暴露会加剧慢性肾脏疾病的进展，但其对急性肾损伤的影响几乎是未知的。在这里，我们研究了慢性尼古丁暴露对急性肾缺血性损伤的影响。我们发现，慢性尼古丁暴露增加了热缺血再灌注引起的肾损伤的程度，证明了形态学变化，血浆肌酐水平的增加，和肾损伤分子-1的表达。我们还发现，慢性尼古丁暴露升高氧化应激的标志物，如硝基酪氨酸以及丙二醛。有趣的是，慢性尼古丁暴露单独增加肾脏的氧化应激和损伤，而没有形态学改变。慢性尼古丁治疗不仅增加了活性氧（ROS）的产生和损伤，而且还加剧了氧化应激诱导的ROS产生，通过NADPH氧化酶和线粒体在培养的肾近端小管细胞。由此产生的氧化应激通过JNK介导的激活蛋白（AP）-1转录因子在体外激活引起损伤。这种机制可能存在于体内，因为JNK及其下游靶点c-jun（AP-1转录因子的一种组分）的磷酸化在暴露于慢性尼古丁的缺血性肾脏中升高。我们的研究结果表明，吸烟可能会使肾脏对缺血性损伤敏感，并可能促进急性肾损伤向慢性肾损伤的进展。
Arany I, Grifoni S, Clark JS, Csongradi E, Maric C, Juncos LA. Chronic nicotine exposure exacerbates acute renal ischemic injury. Am J Physiol Renal Physiol 301: F125-F133, 2011. First published April 20, 2011; doi: 10.1152/ajprenal.00041.2011.-Recent epidemiological reports showed that smoking has a negative impact on renal function and elevates the renal risk not only in the renal patient but perhaps also in the healthy population. Studies suggested that nicotine, a major tobacco alkaloid, links smoking to renal dysfunction. While several studies showed that smoking/chronic nicotine exposure exacerbates the progression of chronic renal diseases, its impact on acute kidney injury is virtually unknown. Here, we studied the effects of chronic nicotine exposure on acute renal ischemic injury. We found that chronic nicotine exposure increased the extent of renal injury induced by warm ischemia-reperfusion as evidenced by morphological changes, increase in plasma creatinine level, and kidney injury molecule-1 expression. We also found that chronic nicotine exposure elevated markers of oxidative stress such as nitrotyrosine as well as malondialdehyde. Interestingly, chronic nicotine exposure alone increased oxidative stress and injury in the kidney without morphological alterations. Chronic nicotine treatment not only increased reactive oxygen species (ROS) production and injury but also exacerbated oxidative stress-induced ROS generation through NADPH oxidase and mitochondria in cultured renal proximal tubule cells. The resultant oxidative stress provoked injury through JNK-mediated activation of the activator protein (AP)-1 transcription factor in vitro. This mechanism might exist in vivo as phosphorylation of JNK and its downstream target c-jun, a component of the AP-1 transcription factor, is elevated in the ischemic kidneys exposed to chronic nicotine. Our results imply that smoking may sensitize the kidney to ischemic insults and perhaps facilitates progression of acute kidney injury to chronic kidney injury.