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Sublytic C5b-9-stimulated Schwann cell survival through PI 3-kinase-mediated phosphorylation of BAD

S Hila1, L Soane, C L Koski

  • 1Department of Neurology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

Glia
|September 26, 2001
PubMed

Insights

Sublytic complement C5b-9 protects Schwann cells from apoptosis by activating the PI3K-Akt pathway. This signaling cascade promotes cell survival, crucial for remyelination in inflammatory neuropathies.

Area of Science:

  • Immunology
  • Neuroscience
  • Cell Biology

Background:

  • Schwann cells are vital for peripheral nerve health and remyelination.
  • Apoptosis (programmed cell death) in Schwann cells can impair nerve repair.
  • The complement system, particularly C5b-9, plays a role in inflammatory and immune responses.

Purpose of the Study:

  • To investigate the role of sublytic C5b-9 in Schwann cell survival.
  • To elucidate the specific signaling pathways involved in C5b-9-mediated protection against apoptosis.
  • To determine the potential therapeutic implications of C5b-9 in nerve injury and repair.

Main Methods:

  • Primary rat Schwann cells were cultured and induced into apoptosis via serum withdrawal.
  • Apoptosis was quantified using TUNEL and FACS analysis.
  • Sublytic C5b-9 was generated using purified components or depleted serum and C7.
  • Involvement of PI3K/Akt and ERK1 pathways was assessed using specific inhibitors (LY294002 and PD098,059).
  • Protein levels of BAD and Bcl-x(L) were analyzed via Western blotting.

Main Results:

  • Serum withdrawal induced significant DNA fragmentation, indicating apoptosis in Schwann cells.
  • Treatment with sublytic C5b-9 significantly rescued Schwann cells from apoptosis.
  • Sublytic C5b-9 activated the PI3K-Akt pathway, evidenced by increased kinase activity and BAD phosphorylation at Ser 136.
  • Inhibition of PI3K-Akt abrogated C5b-9-mediated cell rescue and downstream effects.
  • C5b-9 treatment led to increased expression of the anti-apoptotic protein Bcl-x(L).

Conclusions:

  • Sublytic C5b-9 protects Schwann cells from apoptosis through the PI3K-Akt signaling pathway.
  • Activation of PI3K-Akt leads to BAD phosphorylation and increased Bcl-x(L) expression, promoting cell survival.
  • These findings suggest that C5b-9 may play a beneficial role in preserving Schwann cells during inflammatory neuropathies, potentially aiding remyelination.

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