Journal
STROKE
Volume 40, Issue 8, Pages 2843-2848Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.109.553644
Keywords
HGTD-P; brain; hypoxia-ischemia; apoptosis
Categories
Funding
- National Natural Science Foundation of China [30825039, 30770748]
- Doctoral Program of Ministry of Education of China [20070610092]
- Outstanding Young Scientist' Foundation of Sichuan Province, China [08ZQ026-069]
Ask authors/readers for more resources
Background and Purpose-Human growth and transformation-dependent protein (HGTD-P) is a new proapoptotic protein and an effector of cell death induced by hypoxia-ischemia (HI). The function of HGTD-P has been investigated in human prostate cancer cells and mouse neurons cultured in vitro. However, whether HGTD-P is involved in regulating the apoptosis of rat neurons is not clear, and the relevance of HGTD-P in HI animal models is still unknown. Therefore, in the present study, we tried to elucidate the role that HGTD-P plays in apoptosis of rat neurons subjected to HI, both in culture and in the developing rat brain in vivo. Methods-Samples from primary cultured neurons and postnatal day 10 rat brains with HI were collected. RT-PCR, Western blotting, and immunocytochemistry were used to detect the expression and distribution of rat HGTD-P, cleaved caspase 3, and apoptosis-inducing factor (AIF). MTT assay, DAPI, TUNEL, and flowcytometry were used to detect cell viability and apoptosis. Results-We found that HI upregulated the mRNA and protein levels of HGTD-P in rat neurons in vitro and in vivo. Antisense oligonucleotides (AS) targeted to HGTD-P inhibited the expression of HGTD-P, thus rescuing neuronal viability and attenuating neuronal apoptosis. In addition, we found that HGTD-P played its proapoptotic role by activating caspase 3 and inducing the translocation of AIF to nuclear. Conclusions-Our findings show that HGTD-P plays a proapoptotic role in the developing rat brain after HI and that it may be a potential target in treating HI-induced brain damage. (Stroke. 2009; 40: 2843-2848.)
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available