H2S-induced pancreatic acinar cell apoptosis is mediated via JNK and p38 MAP kinase
| Autor: | Madhav Bhatia, Sharmila Adhikari |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Male
p38 mitogen-activated protein kinases Caspase 3 p38 Apoptosis Sulfides Models Biological p38 Mitogen-Activated Protein Kinases Mitochondrial Proteins Mice Annexin Acinar cell Animals Phosphorylation Extracellular Signal-Regulated MAP Kinases bcl-2-Associated X Protein biology Kinase H2S Cytochrome c JNK Mitogen-Activated Protein Kinases Cytochromes c Cell Biology Articles equipment and supplies Phosphoproteins Molecular biology Pancreas Exocrine Cell biology Enzyme Activation ERK Protein Transport Mitogen-activated protein kinase biology.protein Molecular Medicine JNK Poly(ADP-ribose) Polymerases Apoptosis Regulatory Proteins Carrier Proteins |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | Treatment of pancreatic acinar cells by hydrogen sulphide has been shown to induce apoptosis. However, a potential role of mitogen-activated protein kinases (MAPKs) in this apoptotic pathway remains unknown. The present study examined the role of MAPKs in H(2)S-induced apoptosis in mouse pancreatic acinar cells. Pancreatic acinar cells were treated with 10 microM NaHS (a donor of H(2)S) for 3 hrs. For the evaluation of the role of MAPKs, PD98059, SP600125 and SB203580 were used as MAPKs inhibitors for ERK1/2, JNK1/2 and p38 MAPK, respectively. We observed activation of ERK1/2, JNK1/2 and p38 when pancreatic acini were exposed to H(2)S. Moreover, H(2)S-induced ERK1/2, JNK1/2 and p38 activation were blocked by pre-treatment with their corresponding inhibitor in a dose-dependent manner. H(2)S-induced apoptosis led to an increase in caspase 3 activity and this activity was attenuated when caspase 3 inhibitor were used. Also, the cleavage of caspase 3 correlated with that of poly-(ADP-ribose)-polymerase (PARP) cleavage. H(2)S treatment induced the release of cytochrome c, smac from mitochondria into the cytoplasm, translocation of Bax into mitochondria and decreased the protein level of Bcl-2. Inhibition of ERK1/2 using PD98059 caused further enhancement of apoptosis as evidenced by annexin V staining, while SP600125 and SB203580 abrogated H(2)S-induced apoptosis. Taken together, the data suggest that activation of ERKs promotes cell survival, whereas activation of JNKs and p38 MAP kinase leads to H(2)S-induced apoptosis. |
| Databáze: | OpenAIRE |
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