Elsevier

Neuroscience Letters

Volume 416, Issue 2, 12 April 2007, Pages 144-149
Neuroscience Letters

mHGTD-P mediates hypoxic neuronal cell death via the release of apoptosis-inducing factor

https://doi.org/10.1016/j.neulet.2007.01.073Get rights and content

Abstract

HGTD-P is a pro-apoptotic target protein of hypoxia-inducible factor 1α (HIF-1α). It localizes to mitochondria and induces the mitochondrial permeability transition through its interaction with voltage dependent anion channels when overexpressed. However, the molecular mechanisms responsible for its induction and its downstream effector molecules required during cell death, especially in neuronal cell death by hypoxia, are largely unknown. We performed this work to elucidate the effects of the pro-apoptotic protein HGTD-P on neuronal cell death induced by hypoxia and to investigate the cell death mechanisms activated during this process. In this report, we show that mouse HGTD-P (mHGTD-P) is transcriptionally increased by hypoxia and that its overexpression triggers neuronal cell death with affected cells displaying shrunken cytoplasm and condensed pyknotic nuclei in a caspase-independent manner. In addition, suppression of endogenous mHGTD-P expression by siRNA rescues neuronal cells from hypoxic injury. Finally, we show that mHGTD-P induces the mitochondrial release of apoptosis-inducing factor into the cytoplasm. Taken together, our data suggest that mHGTD-P participates in caspase-independent hypoxic neuronal cell death. Future studies will be necessary in order to determine whether hypoxia-induced mHGTD-P expression has any relevance in an ischemic animal model or clinical hypoxia-induced disorders.

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Acknowledgements

This work was supported by the Neurobiology Research Program from Korea Ministry of Science and Technology and by Korea Science and Engineering Foundation Grant R13-2002-020-01002-0.

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