Oxygen tension regulates the stability of insulin receptor substrate-1 (IRS-1) through caspase-mediated cleavage.

摘要: The insulin and insulin-like growth factor-1 (IGF-1) receptors mediate signaling for energy uptake through receptor substrates (IRSs), which interact with these as well downstream effectors. Oxygen is essential not only ATP production oxidative phosphorylation but also many cellular processes, particularly those involved in homeostasis. oxygen tension vivo significantly lower than that the air can vary widely depending on tissue perfusion consumption. How affects IRSs their functions poorly understood. Our findings indicate transient hypoxia (1% oxygen) leads to caspase-mediated cleavage of IRS-1 without inducing cell death. protein level rebounds rapidly upon return normoxia. Protein tyrosine phosphatases (PTPs) appear be important because was decreased could blocked either H2O2 or vanadate, each inhibits PTPs. Activity Akt, a effector IGF-1 known suppress caspase activation, suppressed hypoxia. Overexpression dominant-negative Akt led even normoxia, overexpression constitutively active partially hypoxia, suggesting hypoxia-mediated suppression may induce cleavage. In conclusion, our study elucidates mechanism by matched available support metabolism.