Activation and expression of ERK, JNK, and p38 MAP-kinases in isolated islets of Langerhans: implications for cultured islet survival.
Isolation and purification of islet cells exposes them to ischemic, osmotic and mechanical stresses. The objective of this study was to determine the roles of the MAP-kinases in islets immediately following isolation. During the first 48 h, activity of JNK1 and JNK2 declined markedly. Activity of p38 increased steadily with time in culture while extracellular signal regulated kinase (ERK) activity declined dramatically within 24 h post-isolation. High p38 activation relative to ERK activation immediately following isolation correlated with a decrease in islet survival after 36 h in culture. Absence and/or transiency of ERK signaling in conjunction with sustained activation of p38 pathway could be an important regulator of cell death in islets during and following their isolation by commonly employed procedures.
Paraskevas
S
S
Department of Surgery, The Montreal General Hospital, Que., Canada.
Aikin
R
R
Maysinger
D
D
Lakey
J R
JR
Cavanagh
T J
TJ
Hering
B
B
Wang
R
R
Rosenberg
L
L
D000293:Adolescent; D000328:Adult; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002469:Cell Separation; D002470:Cell Survival / Q000502:physiology*; D004285:Dogs; D054638:Dual Specificity Phosphatase 1; D004789:Enzyme Activation; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000166:cytology* / Q000201:enzymology*; D016381:Islets of Langerhans Transplantation; D048031:JNK Mitogen-Activated Protein Kinases; D008875:Middle Aged; D048056:Mitogen-Activated Protein Kinase 9; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases / Q000378:metabolism; D054645:Protein Phosphatase 1; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D013552:Swine; D048051:p38 Mitogen-Activated Protein Kinases
D018797:Cell Cycle Proteins; D017874:Immediate-Early Proteins; D011494:Protein Kinases; D048056:Mitogen-Activated Protein Kinase 9; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1; D017027:Protein Tyrosine Phosphatases