TY - JOUR
T1 - Serum albumin protects from cytokine-induced pancreatic beta cell death by a phosphoinositide 3-kinase-dependent mechanism
AU - Kiaer, Caroline
AU - Thams, Peter
N1 - Keywords: 1-Phosphatidylinositol 3-Kinase; Animals; Cell Death; Cell Survival; Cells, Cultured; Cytokines; Cytoprotection; Hydrogen Peroxide; Insulin-Secreting Cells; Male; Mice; Oncogene Protein v-akt; Phosphorylation; Serum Albumin; Signal Transduction
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1007/s12020-009-9161-7
DO - 10.1007/s12020-009-9161-7
M3 - Journal article
C2 - 19277909
SN - 1355-008X
VL - 35
SP - 325
EP - 332
JO - Endocrine
JF - Endocrine
IS - 3
ER -