title: The member of high temperature requirement family HtrA2 participates in neuronal apoptosis after intracerebral hemorrhage in adult rats.
abstract: The members of high-temperature requirement (HtrA) family are evolutionarily conserved serine proteases that combine a trypsin-like protease domain with at least one PDZ interaction domain. HtrA2, a special one, is mainly located in mitochondria and required for maintaining homeostasis. Once released into cytoplasm, HtrA2 contributes to apoptosis via caspase-dependent and -independent pathways. Accumulating evidence has showed its pro-apoptotic effect in cancers and central nervous system (CNS) diseases. However, the distribution and function of HtrA2 in CNS diseases remains to be further explored. To investigate HtrA2's roles in the pathophysiology of intracerebral hemorrhage (ICH), an ICH rat model was established and assessed by behavioral tests. Western blot and immunohistochemistry revealed a remarkable up-regulation of HtrA2 surrounding the hematoma after ICH; and immunofluorescence showed HtrA2 was strikingly increased in neurons, but not in astrocytes and oligodendrocytes. Terminal deoxynucleotidyl transferase-mediated biotinylated-dUTP nick-end labeling staining suggested the involvement of HtrA2 in neuronal apoptosis after ICH. Additionally, HtrA2 co-localized with active-caspase-3 around the hematoma and the expression of active-caspase-3 was parallel with that of HtrA2 in a time-dependent manner. Furthermore, hemin was used to stimulus a neuronal cell line PC12 to mimic ICH model in vitro. We analyzed the relationship of HtrA2 with X-linked inhibitor of apoptosis protein (XIAP) in PC12 cells by Western blot, immunofluorescence and co-immunoprecipitation. The connection of HtrA2 with XIAP was strengthened in apoptotic cells after hemin treatment. Thus, we speculated that HtrA2 might exert an important function in regulating caspase-dependent neuronal apoptosis through interacting with XIAP following ICH.
authors: Department of Osteology, Affiliated Jiangyin People's Hospital of Nantong University, Jiangyin, 214400, Jiangsu, People's Republic of China.
authors: Huiqing
authors: H
authors: Sun
authors: Lei
authors: L
authors: Li
authors: Feng
authors: F
authors: Zhou
authors: Lin
authors: L
authors: Zhu
authors: Kaifu
authors: K
authors: Ke
authors: Xiang
authors: X
authors: Tan
authors: Wei
authors: W
authors: Xu
authors: Ying
authors: Y
authors: Rui
authors: Heyi
authors: H
authors: Zheng
authors: Zhengming
authors: Z
authors: Zhou
authors: Huiguang
authors: H
authors: Yang
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000201:enzymology / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D006406:Hematoma / Q000378:metabolism / Q000473:pathology; D006427:Hemin / Q000494:pharmacology; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000473:pathology*; D016716:PC12 Cells; D021381:Protein Transport / Q000187:drug effects; D011699:Putamen / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068103:Serine-Arginine Splicing Factors; D013696:Temperature; D013997:Time Factors; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; C490770:Tra2b protein, rat; D051636:X-Linked Inhibitor of Apoptosis Protein; D000068103:Serine-Arginine Splicing Factors; D006427:Hemin; D053148:Caspase 3