当前位置： SCI文献检索 > JOURNAL OF NEUROCHEMISTRY期刊下所有文献 > The herpes simplex virus type 2 gene ICP10PK protects from apoptosis caused by nerve growth factor deprivation through inhibition of caspase-3 activation and XIAP up-regulation.

The herpes simplex virus type 2 gene ICP10PK protects from apoptosis caused by nerve growth factor deprivation through inhibition of caspase-3 activation and XIAP up-regulation.

Abstract：

:The herpes simplex virus type 2 (HSV-2) protein ICP10PK has anti-apoptotic activity in virus-infected hippocampal cultures through activation of the Ras/Raf-1/MEK/ERK pathway. To exclude the possible contribution of other viral proteins to cell fate determination, we examined the survival of primary hippocampal cultures and neuronally differentiated PC12 cells transfected with ICP10PK from apoptosis caused by nerve growth factor (NGF) withdrawal. NGF deprivation caused apoptosis in cultures mock-transfected or transfected with the kinase-negative ICP10 mutant p139(TM), but not in ICP10PK-transfected cultures. In one clone (PC47), ICP10PK inhibited caspase-3 activation through up-regulation/stabilization of adenylate cyclase (AC), activation of PKA and MEK, and the convergence of the two pathways on extracellular signal-regulated kinase activation. The anti-apoptotic proteins Bag-1 and Bcl-2 were stabilized and the pro-apoptotic protein Bad was phosphorylated (inactivated). In another clone (PC70), ICP10PK inhibited apoptosis through MEK-dependent up-regulation of the anti-apoptotic protein XIAP (that inhibits the activity of processed caspase-3) and down-regulation of the apoptogenic protein Smac/DIABLO. This may be cell-type specific, but the baculovirus p35 protein did not potentiate the neuroprotective activity of ICP10PK in PC12 cells, suggesting that ICP10PK inhibits both caspase activation and activity. The data indicate that ICP10PK inhibits apoptosis independent of other viral proteins and is a promising neuronal gene therapy platform.

journal_name

J Neurochem

journal_title

Journal of neurochemistry

authors

Wales SQ,Li B,Laing JM,Aurelian L

doi

10.1111/j.1471-4159.2007.04745.x

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

365-79

issue

1

eissn

0022-3042

issn

1471-4159

pii

JNC4745

journal_volume

103

pub_type

杂志文章

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