Satratoxin G-induced apoptosis in PC-12 neuronal cells paper

[Guest guest]

This looks new, its about apoptosis of nerve cells in the nose,

something that happened to me.

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Toxicol Sci. 2008 Sep;105(1):142-52. Epub 2008 Jun 4.

Satratoxin G-induced apoptosis in PC-12 neuronal cells is mediated

by PKR and caspase independent.

Islam Z, Hegg CC, Bae HK, Pestka JJ.

Center for Integrative Toxicology, Michigan State University, East

Lansing, Michigan 48824-1224, USA.

Satratoxin G (SG) is a macrocyclic trichothecene mycotoxin

produced by Stachybotrys chartarum, a mold suggested to play an

etiologic role in damp building-related illnesses. Acute intranasal

exposure of mice to SG specifically induces apoptosis in olfactory

sensory neurons of the nose. The PC-12 rat pheochromocytoma cell model

was used to elucidate potential mechanisms of SG-induced neuronal cell

death. Agarose gel electrophoresis revealed that exposure to SG at 10

ng/ml or higher for 48-h induced DNA fragmentation characteristic of

apoptosis in PC-12 cells. SG-induced apoptosis was confirmed by

microscopic morphology, hypodiploid fluorescence and annexin

V-fluorescein isothiocyanate (FITC) uptake. Messenger RNA expression

of the proapoptotic genes p53, double-stranded RNA-activated protein

kinase (PKR), BAX, and caspase-activated DNAse was significantly

elevated from 6 to 48 h after SG treatment. SG also induced apoptosis

and proapoptotic gene expression in neural growth

factor-differentiated PC-12 cells. Although SG-induced caspase-3

activation, caspase inhibition did not impair apoptosis. Moreover, SG

induced nuclear translocation of apoptosis-inducing factor (AIF), a

known contributor to caspase-independent neuronal cell death.

SG-induced apoptosis was not affected by inhibitors of oxidative

stress or mitogen-activated protein kinases but was suppressed by the

PKR inhibitor C16 and by PKR siRNA transfection. PKR inhibition also

blocked SG-induced apoptotic gene expression and AIF translocation but

not caspase-3 activation. Taken together, SG-induced apoptosis in

PC-12 neuronal cells is mediated by PKR via a caspase-independent

pathway possibly involving AIF translocation.

PMID: 18535002 [PubMed - in process]