Hypothermia-induced increase of oligodendrocyte precursor cells

Possible involvement of plasmalemmal voltage-dependent anion channel 1

Shinya Imada, Masahiro Yamamoto, Kayoko Tanaka, Chika Seiwa, Kenji Watanabe, Yoshimasa Kamei, Shiro Kozuma, Yuji Taketani, Hiroaki Asou

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Hypothermia is believed to suppress cell proliferation by inducing apoptosis/necrosis and phase-specific/nonspecific cell cycle arrest, which are, directly or indirectly, related to a reduced energy supply. Intriguingly, hypothermia is known to improve neurological recovery of animals and humans exposed to focal brain hypoxic-ischemic injury. The underlying mechanism of the neuroprotective effect of hypothermia is unclear, although the prevention of neural cell apoptosis is thought to play a role. Herein we demonstrate that in vitro cell culture of oligodendrocyte precursor cells (OPCs) under conditions of mild hypothermia (31.5°C) results in an increase in cell number relative to cells cultured under normothermic conditions (37°C). Cell cycle analysis, immunoblotting of cyclins, TUNEL assay, and immunocytochemistry of OPC differentiation markers suggest that hypothermia shifts the balance between proliferation and apoptosis/differentiation toward proliferation. A combination of transcriptome analysis, pharmacological intervention, and immunoaffinity-based assays suggests a possible involvement of the Gα13-Rho GTPase Cdc42-ERK1/2 signaling cascade and voltage-dependent anion channel 1 (VDAC1), which associate or dissociate with Gα13 protein at 37°C and 31.5°C, respectively. Immunoelectron microscopy revealed the presence of VDAC1 in the plasma membrane of OPCs. Furthermore, the exogenous addition of impermeable VDAC1 inhibitors enhanced proliferation of OPCs at 37°C. These results may contribute to the elucidation of the mechanism of hypothermic neuroprotection as well as the possible novel role of plasmalemmal VDAC1.

Original languageEnglish
Pages (from-to)3457-3466
Number of pages10
JournalJournal of Neuroscience Research
Volume88
Issue number16
DOIs
Publication statusPublished - 2010 Dec

Fingerprint

Voltage-Dependent Anion Channel 1
Induced Hypothermia
Oligodendroglia
Hypothermia
Apoptosis
G12-G13 GTP-Binding Protein alpha Subunits
rho GTP-Binding Proteins
Cyclins
Immunoelectron Microscopy
Differentiation Antigens
In Situ Nick-End Labeling
Gene Expression Profiling
Neuroprotective Agents
Cell Cycle Checkpoints
Immunoblotting
Cell Differentiation
Cultured Cells
Cell Cycle
Necrosis
Cell Culture Techniques

Keywords

  • Gα13
  • Hypothermic neuroprotection
  • Plasmalemmal VDAC1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Hypothermia-induced increase of oligodendrocyte precursor cells : Possible involvement of plasmalemmal voltage-dependent anion channel 1. / Imada, Shinya; Yamamoto, Masahiro; Tanaka, Kayoko; Seiwa, Chika; Watanabe, Kenji; Kamei, Yoshimasa; Kozuma, Shiro; Taketani, Yuji; Asou, Hiroaki.

In: Journal of Neuroscience Research, Vol. 88, No. 16, 12.2010, p. 3457-3466.

Research output: Contribution to journalArticle

Imada, S, Yamamoto, M, Tanaka, K, Seiwa, C, Watanabe, K, Kamei, Y, Kozuma, S, Taketani, Y & Asou, H 2010, 'Hypothermia-induced increase of oligodendrocyte precursor cells: Possible involvement of plasmalemmal voltage-dependent anion channel 1', Journal of Neuroscience Research, vol. 88, no. 16, pp. 3457-3466. https://doi.org/10.1002/jnr.22520
Imada, Shinya ; Yamamoto, Masahiro ; Tanaka, Kayoko ; Seiwa, Chika ; Watanabe, Kenji ; Kamei, Yoshimasa ; Kozuma, Shiro ; Taketani, Yuji ; Asou, Hiroaki. / Hypothermia-induced increase of oligodendrocyte precursor cells : Possible involvement of plasmalemmal voltage-dependent anion channel 1. In: Journal of Neuroscience Research. 2010 ; Vol. 88, No. 16. pp. 3457-3466.
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