HIF-1 regulation of chondrocyte apoptosis: induction of the autophagic pathway.

摘要: The goal of our investigation was to explore the mechanism by which hypoxia regulates growth plate chondrocyte survival. At low O2 tension, chondrocytes were refractory a staurosporine (i.e., apoptosis-inducing) challenge. To determine whether hypoxic survival due expression HIF-1, we evaluated response HIF silenced cells staurosporine. Both, and control equally sensitive apoptogen learn if resistance mediated proteins autophagic pathway, examined Beclin 1 LC3. Both present in as well N1511 chondrocytes. Moreover, silencing resulted enhanced death. Thus, this gene served maintain activity. Besides serving cytoprotective role, it is known that autophagy can function cell Accordingly, ascertain might also sensitize apoptosis, activated viability following exposure an apoptogen. Treatment with inhibitor 3-methyladenine rendered killing, suggesting sustained promoted We next BID caspase-8. When suppressed, caspase-8 activation BID. Finally, explored relationship between HIF-1 1. noted decrease loss 1-Bcl-2 association maintained upon serum starvation. This study indicates serves regulate both apoptosis.