Involvement of α1β1 integrin in insulin‐like growth factor‐1‐mediated protection of PC12 neuronal processes from tumor necrosis factor‐α‐induced injury

摘要: Insulin-like growth factor 1 receptor (IGF-1R) supports neuronal survival against a wide variety of insults. This includes tumor necrosis factor-alpha (TNFalpha)-mediated damage, which represents one the factors suspected to play role in HIV-associated dementia (HAD). PC12 neurons engineered express human IGF-1R (PC12/IGF-1R) maintain processes on collagen IV for several weeks. However, prolonged treatment with TNFalpha caused degeneration processes, no apparent signs apoptosis. In this process, did not affect IGF-1-mediated phosphorylation IRS-1, IRS-2, Akt, or Erks. addition, PC12/IGF-1R cells were found predominantly alpha1beta1 integrin, has high affinity IV. The specific integrin inhibitor, obtustatin, also loss accompanied by quick cell detachment and extensive presence IGF-1, both TNFalpha-induced obtustatin-induced effectively inhibited. Furthermore, TNFalpha-mediated correlated decreased attachment reduced level consistent surface protein maintenance processes. Thus neuroprotective effects IGF-1 are restricted its antiapoptotic properties but involve an additional mechanism, counteracts negative effect integrin-mediated