H2S-induced pancreatic acinar cell apoptosis is mediated via JNK and p38 MAP kinase.
H2S-induced pancreatic acinar cell apoptosis is mediated via JNK and p38 MAP kinase.
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DOI：
10.1111/j.1582-4934.2008.00318.x
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发表时间：
2008-08
影响因子：
5.3
通讯作者：
Bhatia M
中科院分区：
文献类型：
--
作者：
Adhikari S;Bhatia M
用硫化氢处理胰腺腺泡细胞已被证明可诱导细胞凋亡。然而，有丝分裂原活化蛋白激酶（MAPK）在这一凋亡途径中的潜在作用仍然未知。本研究探讨了MAPKs在H2S诱导的小鼠胰腺腺泡细胞凋亡中的作用。用10 μM NaHS（H2S供体）处理胰腺腺泡细胞3小时。为了评价MAPK的作用，PD 98059、SP 600125和SB 203580分别用作ERK 1/2、JNK 1/2和p38 MAPK的MAPK抑制剂。我们观察到胰腺腺泡暴露于H_2S时，ERK_（1/2）、JNK_（1/2）和p38的激活。H2S诱导的ERK 1/2、JNK 1/2和p38的激活可被相应的抑制剂以剂量依赖的方式阻断。H2S诱导的细胞凋亡导致caspase 3活性增加，而caspase 3抑制剂可减弱caspase 3活性。此外，caspase 3的切割与聚-（ADP-核糖）-聚合酶（PARP）的切割相关。H_2S处理诱导细胞色素c、smac从线粒体释放到细胞质，Bax易位到线粒体，Bcl-2蛋白水平降低。用PD 98059抑制ERK 1/2引起细胞凋亡的进一步增强，如通过膜联蛋白V染色所证明的，而SP 600125和SB 203580废除H2S诱导的细胞凋亡。总之，这些数据表明，ERK的激活促进细胞存活，而JNKs和p38 MAP激酶的激活导致H2S诱导的细胞凋亡。
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 H2S-induced apoptosis in mouse pancreatic acinar cells. Pancreatic acinar cells were treated with 10 μM NaHS (a donor of H2S) 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 H2S. Moreover, H2S-induced ERK1/2, JNK1/2 and p38 activation were blocked by pre-treatment with their corresponding inhibitor in a dose-dependent manner. H2S-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. H2S 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 H2S-induced apoptosis. Taken together, the data suggest that activation of ERKs promotes cell survival, whereas activation of JNKs and p38 MAP kinase leads to H2S-induced apoptosis.
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影响因子：
4.8
作者：
Guyton, KZ;Liu, YS;Holbrook, NJ
通讯作者：
Holbrook, NJ
影响因子：
56.9
作者：
Johnson, GL;Lapadat, R
通讯作者：
Lapadat, R
影响因子：
8
作者：
Grammer, TC;Blenis, J
通讯作者：
Blenis, J
影响因子：
64.8
作者：
Chang, LF;Karin, M
通讯作者：
Karin, M
影响因子：
4.1
作者：
MacFarlane, M;Cohen, GM;Dickens, M
通讯作者：
Dickens, M