Yi Qu1, Meng Mao, Fengyan Zhao, Lin Zhang, Dezhi Mu. 1. Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Abstract
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.
BACKGROUND AND PURPOSE:Humangrowth 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 humanprostate 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 ratHGTD-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.
Authors: Jing-Lan Huang; Yi Qu; Jun Tang; Rong Zou; Shi-Ping Li; Ya-Fei Li; Li Zhang; Bin Xia; De-Zhi Mu Journal: Zhongguo Dang Dai Er Ke Za Zhi Date: 2018-05
Authors: Minna Yli-Karjanmaa; Bettina Hjelm Clausen; Matilda Degn; Hans Gram Novrup; Ditte Gry Ellman; Peter Toft-Jensen; David E Szymkowski; Allan Stensballe; Morten Meyer; Roberta Brambilla; Kate Lykke Lambertsen Journal: Front Neurosci Date: 2019-08-07 Impact factor: 4.677