Get access

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

Authors

  • Jin Ying Wang,

    1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Maja Grabacka,

    1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania
    2. Laboratory of Radiospectroscopy of Cancer and Radiobiology, Faculty of Biotechnology, Jagiellonian University, Krakow, Poland
    Search for more papers by this author
  • Cezary Marcinkiewicz,

    1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Izabella Staniszewska,

    1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Francesca Peruzzi,

    1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Kamel Khalili,

    1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Shohreh Amini,

    1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania
    2. Department of Biology, Temple University School of Medicine, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Krzysztof Reiss

    Corresponding author
    1. Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, Philadelphia, Pennsylvania
    • Center for Neurovirology, Department of Neuroscience, Temple University School of Medicine, 1900 North 12th Street, Biology Life Science Building, Philadelphia, PA 19122
    Search for more papers by this author

Abstract

Insulin-like growth factor 1 receptor (IGF-1R) supports neuronal survival against a wide variety of insults. This includes tumor necrosis factor-α (TNFα)-mediated neuronal damage, which represents one of the factors suspected to play a role in HIV-associated dementia (HAD). PC12 neurons engineered to express human IGF-1R (PC12/IGF-1R) maintain neuronal processes on collagen IV for several weeks. However, prolonged treatment with TNFα caused degeneration of neuronal processes, with no apparent signs of apoptosis. In this process, TNFα did not affect IGF-1-mediated phosphorylation of IRS-1, IRS-2, Akt, or Erks. In addition, PC12/IGF-1R cells were found to express predominantly α1β1 integrin, which has high affinity to collagen IV. The treatment of PC12/IGF-1R neurons with a specific α1β1 integrin inhibitor, obtustatin, also caused loss of neuronal processes, accompanied by a quick cell detachment and extensive apoptosis. In the presence of IGF-1, both TNFα-induced and obtustatin-induced degeneration of neuronal processes were effectively inhibited. Furthermore, TNFα-mediated neuronal degeneration correlated with decreased attachment of PC12/IGF-1R cells to collagen IV and with a reduced level of α1β1 integrin, consistent with a role for this surface protein in the maintenance of neuronal processes. Thus the neuroprotective effects of IGF-1 are not restricted to its antiapoptotic properties but also involve an additional neuroprotective mechanism, by which IGF-1 counteracts the negative effect of TNFα on α1β1 integrin-mediated attachment to collagen IV. © 2005 Wiley-Liss, Inc.

Get access to the full text of this article

Ancillary