The acinar cell and early pancreatitis responses.
The acinar cell and early pancreatitis responses.
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DOI：
10.1016/j.cgh.2009.07.036
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发表时间：
2009-11
影响因子：
12.6
通讯作者：
Thrower, Edwin
中科院分区：
文献类型：
--
作者：
Gorelick, Fred S.;Thrower, Edwin
胰腺腺泡细胞引起的病理反应似乎在急性胰腺炎的发生中起着重要作用。使腺泡细胞对有害刺激敏感的环境因素可能在许多形式的胰腺炎中起关键作用，包括酗酒引起的胰腺炎。腺泡细胞内酶原的激活和分泌的抑制是关键的，但了解甚少，早期胰腺炎事件。虽然有确凿的证据表明胰蛋白酶原激活与胰腺炎有关，但其他酶原的重要性研究较少。初步研究表明，胰蛋白酶可能被激活的机制是不同于其他酶原。此外，与小肠不同，它可能不会催化其他酶原的活化。这些特征可能会影响旨在抑制蛋白酶治疗胰腺炎的策略。需要特定的细胞内信号来激活腺泡细胞中的胰腺炎通路。最重要的是钙。最近的研究表明，通过内质网中的特定钙通道释放钙是细胞溶质钙发生病理性升高的手段。虽然钙信号异常的目标是未知的，钙依赖性磷酸酶钙调神经磷酸酶，可能起到这样的作用。最后，最近的研究表明，急性酸负荷可能会使腺泡细胞对胰腺炎反应敏感。旨在预防或逆转酸负荷对胰腺的影响的疗法可能对治疗很重要。
Pathologic responses arising from the pancreatic acinar cell appear to have a central role in initiating acute pancreatitis. Environmental factors that sensitize the acinar cell to harmful stimuli likely have a critical role in many forms of pancreatitis, including that induced by alcohol abuse. Activation of zymogens within the acinar cell and an inhibition of secretion are critical, but poorly understood, early pancreatitis events. While there is firm evidence relating trypsinogen activation to pancreatitis, the importance of other zymogens has been less studied. Preliminary studies suggest that trypsin may be activated by mechanisms that are distinct from other zymogens. Further, unlike the small intestine, it may not catalyze the activation of other zymogens. These features could affect strategies aimed at inhibiting proteases to treat pancreatitis. Specific intracellular signals are required to activate pancreatitis pathways in the acinar cell. The most important is calcium. Recent studies have suggested that calcium release through specific calcium channels in the endoplasmic reticulum is the means by which pathological elevations in cytosolic calcium occur. Although the targets of abnormal calcium signaling are unknown, calcineurin, a calcium-dependent phosphatase, may serve such a role. Finally, recent work suggests that an acute acid load might sensitize the acinar cell to pancreatitis responses. Therapies aimed at preventing or reversing the effects of an acid load on the pancreas may be important for treatment.
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影响因子：
24.5
作者：
Noble MD;Romac J;Vigna SR;Liddle RA
通讯作者：
Liddle RA
DOI：
10.1152/ajpgi.00500.2006
发表时间：
2007-06-01
影响因子：
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作者：
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DOI：
10.1073/pnas.0503215102
发表时间：
2005-10-04
影响因子：
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作者：
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通讯作者：
Gorelick, FS
影响因子：
29.4
作者：
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通讯作者：
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影响因子：
9.8
作者：
Nair, S;Yadav, D;Pitchumoni, CS
通讯作者：
Pitchumoni, CS