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

[1] Transcriptional regulation of the heme oxygenase-1 gene via the stress response element pathway
Alam, J
Cook, JL
[J]. CURRENT PHARMACEUTICAL DESIGN, 2003, 9 (30) : 2499 - 2511
[2] p66shc inhibits pro-survival epidermal growth factor receptor/ERK signaling during severe oxidative stress in mouse renal proximal tubule cells
Arany, Istvan
Faisal, Amir
Nagamine, Yoshikuni
Safirstein, Robert L.
[J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (10) : 6110 - 6117
[3] Coenzyme Q10 protects renal proximal tubule cells against nicotine-induced apoptosis through induction of p66shc-dependent antioxidant responses
Arany, Istvan
Carter, Anthony
Hall, Samuel
Fulop, Tibor
Dixit, Mehul
[J]. APOPTOSIS, 2017, 22 (02) : 220 - 228
[4] Arany I, 2013, ANTICANCER RES, V33, P3119
[5] Chronic nicotine exposure augments renal oxidative stress and injury through transcriptional activation of p66shc
Arany, Istvan
Clark, Jeb
Reed, Dustin K.
Juncos, Luis A.
[J]. NEPHROLOGY DIALYSIS TRANSPLANTATION, 2013, 28 (06) : 1417 - 1425
[6] Arany I, 2011, ANTICANCER RES, V31, P3267
[7] Chronic nicotine exposure exacerbates acute renal ischemic injury
Arany, Istvan
Grifoni, Samira
Clark, Jeb S.
Csongradi, Eva
Maric, Christine
Juncos, Luis A.
[J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2011, 301 (01) : F125 - F133
[8] p66SHC-mediated mitochondrial dysfunction in renal proximal tubule cells during oxidative injury
Arany, Istvan
Faisal, Amir
Clark, Jeb S.
Vera, Trinity
Baliga, Radhakrishna
Nagamine, Yoshikuni
[J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2010, 298 (05) : F1214 - F1221
[9] Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells
Chen, CY
Jang, JH
Li, MH
Surh, YJ
[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 331 (04) : 993 - 1000
[10] Cheng L, 2015, INT J CLIN EXP MED, V8, P10420

← 1 2 3 →