H2S‐induced pancreatic acinar cell apoptosis is mediated via JNK and p38 MAP Kinase

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 μM NaHS (a donor of H 2 S) for 3 hours. 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 pretreatment with their corresponding inhibitor in a dose‐dependent manner. H 2 S‐induced apoptosis led to an increase in caspase 3 activities 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.