Document Detail

The member of high temperature requirement family HtrA2 participates in neuronal apoptosis after intracerebral hemorrhage in adult rats.
MedLine Citation:
PMID:  23413020     Owner:  NLM     Status:  Publisher    
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.
Huiqing Sun; Lei Li; Feng Zhou; Lin Zhu; Kaifu Ke; Xiang Tan; Wei Xu; Ying Rui; Heyi Zheng; Zhengming Zhou; Huiguang Yang
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-15
Journal Detail:
Title:  Journal of molecular histology     Volume:  -     ISSN:  1567-2387     ISO Abbreviation:  J. Mol. Histol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101193653     Medline TA:  J Mol Histol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Osteology, Affiliated Jiangyin People's Hospital of Nantong University, Jiangyin, 214400, Jiangsu, People's Republic of China.
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