Hyperglycemia Regulates TXNIP/TRX/ROS Axis via p38 MAPK and ERK Pathways in Pancreatic Cancer

ISSN: 1873-5576 (Online)
ISSN: 1568-0096 (Print)


Volume 14, 9 Issues, 2014


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Texas Tech University Health Sciences Center
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Hyperglycemia Regulates TXNIP/TRX/ROS Axis via p38 MAPK and ERK Pathways in Pancreatic Cancer

Author(s): Wei Li, Zheng Wu, Qingyong Ma, Jiangbo Liu, Qinhong Xu, Liang Han, Wanxing Duan, Yunfu Lv, Fengfei Wang, Katie M. Reindl and Erxi Wu

Affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an 710061, China.

Abstract

Approximately 85% of pancreatic cancer patients suffer from glucose intolerance or even diabetes because high glucose levels can contribute to oxidative stress which promotes tumor development. As one of the reactive oxygen species (ROS)-regulating factors, thioredoxin-interacting protein (TXNIP), is involved in the maintenance of thioredoxin (TRX)-mediated redox regulation. In this study, we demonstrated that high glucose levels increased the expression of TXNIP in time- and concentration-dependent manners and modulated the activity of TRX and ROS production in pancreatic cancer cells, BxPC-3 and Panc-1. We also found that glucose activated both p38 MAPK and ERK pathways and inhibitors of these pathways impaired the TXNIP/TRX/ROS axis. Knockdown of TXNIP restored TRX activity and decreased ROS production under high glucose conditions. Moreover, we observed that the integrated optical density (IOD) of TXNIP staining as well as the protein and mRNA expression levels of TXNIP were higher in the tumor tissues of pancreatic cancer patients with diabetes. Taken together, these results indicate that hyperglycemia-induced TXNIP expression is involved in diabetes-mediated oxidative stress in pancreatic cancer via p38 MAPK and ERK pathways.

Keywords: Glucose, MAPK pathway, pancreatic cancer, ROS, TXNIP.

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Article Details

Volume: 14
Issue Number: 4
First Page: 348
Last Page: 356
Page Count: 9
DOI: 10.2174/1568009614666140331231658
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