Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Han, Y; Chen, YS; Liu, Z; Bodyak, N; Rigor, D; Bisping, E; Pu, WT; Kang, PM.
Overexpression of HAX-1 protects cardiac myocytes from apoptosis through caspase-9 inhibition.
Circ Res. 2006; 99(4):415-423
Doi: 10.1161/01.RES.0000237387.05259.a5
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- Co-Autor*innen der Med Uni Graz
- Bisping Egbert Hubertus
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- Abstract:
- Caspase-9 is a critical regulator of mitochondria-mediated apoptosis. We found that adult cardiac myocytes, but not nonmyocytes, have high caspase-9 expression, and exhibit relative resistance to caspase-9-induced cell death. Thus, we hypothesized that cardiac myocytes possess factors that resist apoptosis. Through a yeast two-hybrid screening of adult human heart cDNA library, we identified HS-1 associated protein-1 (HAX-1), a 35-kD BH-domain containing protein localized to the mitochondria as one of the molecules that interacts with caspase-9. Recombinant HAX-1 protein inhibited caspase-9 processing in a dose-dependent manner in a cell-free caspase activation assay. Overexpression of HAX-1 in adult cardiac myocytes conferred 30% protection from apoptosis as compared with the control. Suppression of HAX-1 expression using siRNA-HAX-1 resulted in significant cell death in adult cardiac myocytes, suggesting the importance of HAX-1 in cardiac myocyte resistance to apoptotic stimulation. On apoptotic stimulation, some caspase-9 translocated to the mitochondria and co-localized with HAX-1, confirming the spatial proximity of caspase-9 and HAX-1. In summary, HAX-1 is a newly identified anti-apoptotic factor and its mechanism of action is through caspase-9 inhibition.
- Find related publications in this database (using NLM MeSH Indexing)
- Adaptor Proteins, Signal Transducing -
- Adult -
- Animals -
- Apoptosis - physiology
- Caspase 9 -
- Caspases - deficiency Caspases - metabolism
- Enzyme Activation -
- Female -
- Humans -
- Mice -
- Mice, Knockout -
- Mitochondria, Heart -
- Muscle Cells - cytology Muscle Cells - physiology
- Proteins - genetics Proteins - isolation and purification Proteins - metabolism
- Rats -
- Rats, Sprague-Dawley -
- Recombinant Proteins - isolation and purification Recombinant Proteins - metabolism
- Find related publications in this database (Keywords)
- apoptosis
- cardiac myocytes
- caspase
- HAX-1
- mitochondria