The Receptor for Advanced Glycation End-Products (RAGE) Protects Pancreatic Tumor Cells Against Oxidative Injury

Autor: Michael T. Lotze, Rui Kang, Daolin Tang, Kristen M. Livesey, Nicole E. Schapiro, Herbert J. Zeh
Rok vydání: 2011
Předmět:
medicine.medical_specialty
Programmed cell death
Cell Survival
Physiology
Blotting
Western
Receptor for Advanced Glycation End Products
Clinical Biochemistry
Apoptosis
Biology
Real-Time Polymerase Chain Reaction
medicine.disease_cause
Biochemistry
RAGE (receptor)
Mice
Glycation
Cell Line
Tumor
Internal medicine
Autophagy
medicine
Animals
Humans
Receptors
Immunologic
Molecular Biology
Cell damage
Forum Original Research Communications DAMPs (A. Rubartelli and M.T. Lotze
Eds.)
General Environmental Science
chemistry.chemical_classification
Reactive oxygen species
NF-kappa B
Hydrogen Peroxide
Cell Biology
medicine.disease
Pancreatic Neoplasms
Oxidative Stress
Endocrinology
chemistry
Cancer research
General Earth and Planetary Sciences
RNA Interference
Signal transduction
Oxidative stress
Signal Transduction
Zdroj: Antioxidants & Redox Signaling. 15:2175-2184
ISSN: 1557-7716
1523-0864
Popis: Reactive oxygen species, including hydrogen peroxide (H2O2), 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 H2O2-induced pancreatic tumor cell damage. We found that exposure of pancreatic tumor cells to H2O2 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 H2O2-induced oxidative injury. Moreover, we demonstrate that RAGE is a positive feedback regulator for NF-κB as knockdown of RAGE decreased H2O2-induced activity of NF-κB. Taken together, these results suggest that RAGE is an important regulator of oxidative injury. Antioxid. Redox Signal. 15, 2175–2184.
Databáze: OpenAIRE
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