Accession Number:

ADA601932

Title:

MeHG Stimulates Antiapoptotic Signaling in Stem Cells

Descriptive Note:

Final rept. 1 Jul 2009-30 Jun 2011

Corporate Author:

KENNEDY KRIEGER INST INC BALTIMORE MD HUGO W MOSER RESEARCH INST

Personal Author(s):

Report Date:

2011-09-01

Pagination or Media Count:

23.0

Abstract:

The aim of this project was to determine if induction of Hairless Hr by sub lethal levels of toxicants, including methyl mercury, could alter brain development through an aberrant inactivation of the apoptosis pathway. Neurons not making synaptic connections undergo apoptosis. Consequently, inactivation of apoptosis could potentially allow the formation of excess or erroneous synaptic connections resulting in impaired neurodevelopment. We found that Hr expression was rapidly and consistently increased at low levels of toxicant exposure. Overexpression of Hr through transfection assays resulted in significant improvement of viability, lower levels of apoptosis, and lower expression of the pro-apoptotic proteins bax, p53 and CHOP. The role of Hr in the attenuation of apoptosis was confirmed in Hr KO mice exposed to ethanol and Trimethyl tin. Furthermore, it was determined that Hr was functioning through a p53 dependent pathway. In summary, our studies suggest the possible involvement of Hr in methyl mercury mediated neurotoxicity.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE