Background: Neurons are more likely to die through apoptosis in the immature brain after injury whereas adult neurons in the mature brain die by necrosis. Several studies have suggested that this maturational change in the mechanism of cell death is regulated, in part, by thyroid hormone. We examined the involvement of the hairless (Hr) gene which has been suspected of having a role in cell cycle regulation and apoptosis in the hair follicle and is strongly regulated by the thyroidhorm one in the brain. Methodology: Forced expression of Hr by transfection decreased the number of apoptotic nuclei, levels of caspase-3activity, and cytosolic cytochrome C in COS cells exposed to staurosporine and tunicamyc in. Similarly, capsase-3 activity waslower and the decrease in mitochondrial membrane potential was smaller in cultures of adult cerebellar granule neurons from wild type mice compared to Hr knockout mice induced to undergo apoptosis. In vivo, apoptosis as detected bypositive TUNEL labeling and caspase 3 activity was lower in wild-type mice compared to Hr knockouts after exposure totrimethyltin. Hr expression lowered levels of p53, p53 mediated reporter gene activity, and lower levels of the pro-apoptoticBcl2 family member Bax in COS cells. Finally, Hr expression did not attenuate apoptosis in mouse embryonic fibroblasts fromp53 knockout mice but was effective in mouse embryonic fibroblasts from wild type mice.Conclusions/Significance: Overall, our studies demonstrate that Hr evokes an anti-apoptotic response by repressing expression of p53 and pro-apoptotic events regulated by p53.© 2010 O'Driscoll, Bressler.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Agricultural and Biological Sciences(all)