Cholecystokinin-8-induced hypoplasia of the rat pancreas: influence of nitric oxide on cell proliferation and programmed cell death.
Cholecystokinin-8-induced hypoplasia of the rat pancreas: influence of nitric oxide on cell proliferation and programmed cell death.
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DOI：
10.1111/j.1742-7843.2004.pto_950406.x
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发表时间：
2004-10
影响因子：
3.1
通讯作者：
L. Trulsson;T. Gasslander;J. Svanvik
中科院分区：
文献类型：
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作者：
L. Trulsson;T. Gasslander;J. Svanvik
胆囊收缩素 8 (CCK-8) 诱导的胰腺发育不全的背景尚不清楚。为了加深我们的理解，我们研究了一氧化氮和 NF-κB 在大鼠中的作用。 CCK-8 注射 4 天，以一种已知会导致发育不全的方式注射，一氧化氮的形成要么通过 N(omega)-硝基-L-精氨酸 (L-NNA) 减少，要么通过 S-亚硝基-N-乙酰青霉胺 (SNAP) 增加。通过 ELISA 检测对 NF-kappaB 的激活进行定量，通过掺入 [(3)H]-胸苷来可视化腺泡、腺泡中心和导管细胞中 caspase-3 和组蛋白相关 DNA 片段的凋亡以及有丝分裂活性。还研究了胰腺组织学和重量以及蛋白质和 DNA 含量。间歇性 CCK 注射可降低胰腺重量、蛋白质和 DNA 含量，并增加细胞凋亡、腺泡细胞增殖和核因子 kappaB (NF-kappaB) 激活。它还引起腺泡细胞空泡化。 L-NNA 对内源性一氧化氮形成的抑制进一步增加了细胞凋亡和 NF-κB 激活，但阻止了腺泡细胞的增殖和空泡形成。 DNA含量没有进一步降低。 SNAP 与 CCK-8 一起服用会增加细胞凋亡和其他细胞死亡途径，增加腺泡细胞的增殖并强烈降低胰腺中的 DNA 含量。组织学检查显示任何组均未出现炎症。我们得出的结论是，在 CCK-8 诱导的胰腺发育不全期间，内源性形成的一氧化氮抑制细胞凋亡，但增加非细胞凋亡途径的细胞死亡，并刺激腺泡细胞的再生。外源性一氧化氮通过增加凋亡和非凋亡细胞死亡和细胞更新来增强腺泡细胞的更新。在这种情况下，NF-κB 激活似乎既不会抑制细胞凋亡，也不会促进细胞增殖。
The background of cholecystokinin-8 (CCK-8)-induced hypoplasia in the pancreas is not known. In order to increase our understanding we studied the roles of nitric oxide and NF-kappaB in rats. CCK-8 was injected for 4 days, in a mode known to cause hypoplasia, and the nitric oxide formation was either decreased by means of N(omega)-nitro-L-arginine (L-NNA) or increased by S-nitroso-N-acetylpencillamine (SNAP). The activation of NF-kappaB was quantified by ELISA detection, apoptosis with caspase-3 and histone-associated DNA-fragmentation and mitotic activity in the acinar, centroacinar and ductal cells were visualized by the incorporation of [(3)H]-thymidine. Pancreatic histology and weight as well as protein- and DNA contents were also studied. Intermittent CCK injections reduced pancreatic weight, protein and DNA contents and increased apoptosis, acinar cell proliferation and nuclear factor kappaB (NF-kappaB) activation. It also caused vacuolisation of acinar cells. The inhibition of endogenous nitric oxide formation by L-NNA further increased apoptosis and NF-kappaB activation but blocked the increased proliferation and vacuolisation of acinar cells. The DNA content was not further reduced. SNAP given together with CCK-8 increased apoptosis and other pathways of cell death, raised proliferation of acinar cells and strongly reduced the DNA content in the pancreas. Histological examination showed no inflammation in any group. We conclude that during CCK-8-induced pancreatic hypoplasia, endogenously formed nitric oxide suppresses apoptosis but increases cell death along non-apoptotic pathways and stimulates regeneration of acinar cells. Exogenous nitric oxide enhances the acinar cell turnover by increasing both apoptotic and non-apoptotic cell death and cell renewal. In this situation NF-kappaB activation seems not to inhibit apoptosis nor promote cell proliferation.