Differential responses of pancreatic β-cells to ROS and RNS. Am J Physiol Endocrinol Metab 2013 Mar 15;304(6):E614-22
Date
01/17/2013Pubmed ID
23321474Pubmed Central ID
PMC3602694DOI
10.1152/ajpendo.00424.2012Scopus ID
2-s2.0-84877276240 (requires institutional sign-in at Scopus site) 33 CitationsAbstract
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) direct the activation of distinct signaling pathways that determine cell fate. In this study, the pathways activated and the mechanisms by which ROS and RNS control the viability of pancreatic β-cells were examined. Although both nitric oxide and hydrogen peroxide (H₂O₂) induce DNA damage, reduce cell viability, and activate AMPK, the mechanisms of AMPK activation and cell death induction differ between each reactive species. Nitric oxide activates the unfolded protein and heat shock responses and MAPK kinase signaling, whereas H₂O₂ stimulates p53 stabilization and poly(ADP-ribose) polymerase (PARP) activation but fails to induce the unfolded protein or heat shock responses or MAPK activation. The control of cell fate decisions is selective for the form of stress. H₂O₂-mediated reduction in β-cell viability is controlled by PARP, whereas cell death in response to nitric oxide is PARP independent but associated with the nuclear localization of GAPDH. These findings show that both ROS and RNS activate AMPK, induce DNA damage, and reduce cell viability; however, the pathways controlling the responses of β-cells are selective for the type of reactive species.
Author List
Meares GP, Fontanilla D, Broniowska KA, Andreone T, Lancaster JR Jr, Corbett JAAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis Regulatory Proteins
Cell Cycle Proteins
Cell Line
Cell Nucleus
Cell Survival
DNA Damage
Heat-Shock Response
Insulin
Insulin-Secreting Cells
MAP Kinase Signaling System
Male
Nuclear Proteins
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Protein Transport
RNA-Binding Proteins
Rats
Rats, Sprague-Dawley
Reactive Nitrogen Species
Reactive Oxygen Species
Tissue Culture Techniques
Transcription Factors
Unfolded Protein Response
