Serum albumin protects from cytokine-induced pancreatic beta cell death by a phosphoinositide 3-kinase-dependent mechanism.
The present study was undertaken to investigate the biological activity of serum albumin when pancreatic beta cells were challenged by cytokines and pro-apoptotic reactive oxygen species like H(2)O(2). Culture of mouse islets or INS-1E beta cells for 24 h in the presence of H(2)O(2) (25 micromol/l) increased cell death. This demise was prevented by serum albumin, dependent on its free sulfhydryl group, emphasizing that albumin may scavenge H(2)O(2) due to its antioxidant properties. Culture for 48 h with a cytokine mixture of IL-1beta (160 pg/ml), IFN-gamma (200 ng/ml), and TNF-alpha (2 ng/ml) revealed that albumin, also protected against cytokine-induced death of both mouse islets and INS-1E beta cells. This protective effect against cytokine-induced beta cell death was, however, not dependent on albumins free sulfhydryl group, but was inhibited by the phosphoinositide 3-kinase (PI3K) inhibitors LY294002 (25 micromol/l) and wortmannin (1 micromol/l), suggesting that albumin may rescue beta cells from cytokine-induced cell death by activation of PI3K. In accordance, albumin stimulated phosphorylation of Akt, a down-stream target for PI3K. In conclusion, it is suggested that albumin may be a survival factor for pancreatic beta cells through scavenging of reactive oxygen species and by PI3K-dependent activation of Akt.
Kiaer
Caroline
C
Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen N, Denmark.
Thams
Peter
P
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology*; D019610:Cytoprotection / Q000187:drug effects*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D012709:Serum Albumin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D016207:Cytokines; D012709:Serum Albumin; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt