The receptor for advanced glycation end-products (RAGE) protects pancreatic tumor cells against oxidative injury

Rui Kang, Daolin Tang, Kristen M. Livesey, Nicole E. Schapiro, Michael T. Lotze, Herbert J. Zeh

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Reactive oxygen species, including hydrogen peroxide (H 2O 2), can cause toxicity and act as signaling molecules in various pathways regulating both cell survival and cell death. However, the sequence of events between the oxidative insult and cell damage remains unclear. In the current study, we investigated the effect of oxidative stress on activation of the Receptor for Advanced Glycation End-products (RAGE) and subsequent protection against H 2O 2-induced pancreatic tumor cell damage. We found that exposure of pancreatic tumor cells to H 2O 2 provoked a nuclear factor kappa B (NF-κB)-dependent increase in RAGE expression. Further, suppression of RAGE expression by RNA interference increased the sensitivity of pancreatic tumor cells to oxidative injury. Furthermore, targeted knockdown of RAGE led to increased cell death by apoptosis and diminished cell survival by autophagy during H 2O 2-induced oxidative injury. Moreover, we demonstrate that RAGE is a positive feedback regulator for NF-κB as knockdown of RAGE decreased H 2O 2-induced activity of NF-κB. Taken together, these results suggest that RAGE is an important regulator of oxidative injury.

Original languageEnglish (US)
Pages (from-to)2175-2184
Number of pages10
JournalAntioxidants and Redox Signaling
Volume15
Issue number8
DOIs
StatePublished - Oct 15 2011
Externally publishedYes

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Tumors
Cells
Wounds and Injuries
Neoplasms
NF-kappa B
Cell death
Cell Survival
Cell Death
Oxidative stress
Autophagy
RNA Interference
Advanced Glycosylation End Product-Specific Receptor
Hydrogen Peroxide
Toxicity
Reactive Oxygen Species
Oxidative Stress
Chemical activation
RNA
Apoptosis
Feedback

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

The receptor for advanced glycation end-products (RAGE) protects pancreatic tumor cells against oxidative injury. / Kang, Rui; Tang, Daolin; Livesey, Kristen M.; Schapiro, Nicole E.; Lotze, Michael T.; Zeh, Herbert J.

In: Antioxidants and Redox Signaling, Vol. 15, No. 8, 15.10.2011, p. 2175-2184.

Research output: Contribution to journalArticle

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