ICP10PK inhibits calpain-dependent release of apoptosis-inducing factor and programmed cell death in response to the toxin MPP+

S. Q. Wales, J. M. Laing, Ling-Xin Chen, L. Aurelian

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Apoptosis is a widely accepted component of the pathogenesis of Parkinson's disease (PD), a debilitating neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. However, additional death programs were implicated, and current understanding of the cycle of intracellular events that leads to the demise of these neuronJis limited. Gene therapy strategies were proposed to inhibit apoptosis, but they have met with relatively limited success. Here we report that the antiapoptotic herpes simplex virus type 2 gene ICP10PK protects neuronally differentiated PC12 cells from death caused by 1-methyl-4-phenylpyridinium (in vitro PD model) through inhibition of calpain I activation and the resulting inhibition of Bax translocation to the mitochondria, apoptosis-inducing factor release and caspase-3 activation. Neuroprotection is through ICP10PK-mediated activation of the PI3-K/Akt survival pathway and upregulation/stabilization of the antiapoptotic protein Bcl-2 and the cytoprotective chaperone heat-shock protein 70.

Original languageEnglish (US)
Pages (from-to)1397-1409
Number of pages13
JournalGene Therapy
Volume15
Issue number20
DOIs
StatePublished - Jul 18 2008
Externally publishedYes

Fingerprint

Apoptosis Inducing Factor
Calpain
Parkinson Disease
Cell Death
1-Methyl-4-phenylpyridinium
Apoptosis
HSP70 Heat-Shock Proteins
Human Herpesvirus 2
Dopaminergic Neurons
PC12 Cells
Substantia Nigra
Caspase 3
Neurodegenerative Diseases
Genetic Therapy
Mitochondria
Up-Regulation
Genes
Proteins
In Vitro Techniques
Neuroprotection

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Cite this

ICP10PK inhibits calpain-dependent release of apoptosis-inducing factor and programmed cell death in response to the toxin MPP+. / Wales, S. Q.; Laing, J. M.; Chen, Ling-Xin; Aurelian, L.

In: Gene Therapy, Vol. 15, No. 20, 18.07.2008, p. 1397-1409.

Research output: Contribution to journalArticle

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