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  2. Mitochondria oxidative stress mediated nicotine-promoted activation of pancreatic stellate cells by regulating mitochondrial dynamics

Mitochondria oxidative stress mediated nicotine-promoted activation of pancreatic stellate cells by regulating mitochondrial dynamics

  • Toxicol In Vitro. 2022 Oct;84:105436. doi: 10.1016/j.tiv.2022.105436.
Yue Yuan 1 Zhiren Li 1 Miaomiao Li 1 Tong Jin 1 Xiaoyun Zhang 1 Xinjuan Liu 2 Jianyu Hao 3
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Chaoyang District, Beijing 100020, China.
  • 2 Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Chaoyang District, Beijing 100020, China. Electronic address: lxjw2012@126.com.
  • 3 Department of Gastroenterology, Beijing Chaoyang Hospital, Capital Medical University, Chaoyang District, Beijing 100020, China. Electronic address: haojianyu@ccmu.edu.cn.
Abstract

Nicotine, one of the main ingredients of cigarettes, promotes activation of pancreatic stellate cells(PSCs) and exacerbates pancreatic fibrosis in previous studies. Here we focus on the inner relationship between mitochondrial oxidative stress and mitochondrial dynamics to explore the possible mechanism. Primary human PSCs were stimulated by nicotine. The effect of nicotine on oxidative stress and mitochondrial dynamics was analyzed by Reactive Oxygen Species (ROS) assay, quantitative Real-Time PCR, and western blotting. Mitochondrial morphology was observed. Antioxidant and small interfering RNA transfection were applied to explore the interrelationship between oxidative stress and mitochondrial dynamics, as well as its effect on PSCs activation. Nicotine exposure significantly increased Intracellular and mitochondrial ROS of hPSCs and promoted mitochondrial fission by upregulating dynamin-related protein 1(DRP1). Knockdown Drp1 reversed mitochondrial fragmentation and hPSCs activation that promoted by nicotine, but fail to alleviate oxidative stress. A mitochondrial-targeted antioxidant could reverse all the above changes. Our finding suggests that mitochondria oxidative stress mediated nicotine-promoted activation of PSCs by inducing Drp1-mediated mitochondrial fission, provides a new perspective on the possible mechanism by which nicotine affects PSCs, and reveals a potential therapeutic strategy.

Keywords

Mitochondrial dynamics; Nicotine; Oxidative stress; Pancreatic stellate cells.

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