Nicotine Exposure Augments Renal Toxicity of 5-aza-cytidine Through p66shc: Prevention by Resveratrol

被引：7

作者：

Arany, Istvan ^{[1
]}

Hall, Samuel ^{[1
]}

Faisal, Amir ^{[2
]}

Dixit, Mehul ^{[1
]}

机构：

[1] Univ Mississippi, Med Ctr, Dept Pediat, Div Pediat Nephrol, Jackson, MS 39216 USA

[2] Lahore Univ Management Sci, Lahore, Pakistan

来源：

ANTICANCER RESEARCH | 2017年 / 37卷 / 08期

关键词：

5-aza-cytidine; nicotine; renal-toxicity; p66shc; resveratrol; PROXIMAL TUBULE CELLS; CHRONIC KIDNEY-DISEASE; OXIDATIVE STRESS; INJURY; PROGRESSION; ACTIVATION; SMOKING; PATHWAY; INDUCTION; GENE;

D O I：

10.21873/anticanres.11793

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background/Aim: We have shown that either chronic nicotine (NIC) exposure or 5-aza-cytidine (AZA) augments oxidative stress-dependent injury through stimulating p66shc in renal cells. Hence, NIC could exacerbate adverse effects of AZA while antioxidants such as resveratrol (RES) could prevent it. Materials and Methods: Renal proximal tubule cells (NRK52E) were treated with 20 mu M RES prior to 200 mu M NIC plus 100 nM AZA and cell injury (LDH release) was determined. Reporter luciferase assays determined p66shc activation and RES-induced antioxidant responses. Genetic manipulations identified the mechanism of RES action. Results: NIC exacerbated AZA-dependent injury via augmenting p66shc transcription. While RES suppressed NIC+AZA-mediated injury, -surprisingly- it further enhanced activity of the p66shc promoter. RES protected cells via the cytoplasmic p66shc/Nrf2/heme oxygenase-1 (HO-1) axis. Conclusion: RES can protect the kidney from adverse effects of NIC in patients undergoing anticancer therapy.

引用

页码：4075 / 4079

页数：5

共 27 条

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