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分子途径引物——半胱天冬酶途径。

Primers on molecular pathways--caspase pathway.

作者信息

Lomberk Gwen, Urrutia Raul

机构信息

Division of Gastroenterology, Mayo Clinic, Rochester, MN 55905, USA.

出版信息

Pancreatology. 2009;9(1-2):6-8. doi: 10.1159/000178860. Epub 2008 Dec 12.

Abstract

Apoptosis, or programmed cell death, is a physiological process of cellular autodestruction, or cell suicide. This process is strictly controlled in response to integrity of pro-death signaling and plays critical roles in development, maintenance of homeostasis and host defense in multicellular organisms. As pancreatologists, apoptosis plays a central role in the pancreas and its disease states, from diabetes to pancreatitis to pancreatic cancer. In pancreatic beta-cells, apoptotic cell death is involved in the pathogenesis of diabetes, as signals from death receptors and DNA damage have been widely accepted as being triggers of apoptosis in beta-cells. During acute pancreatitis, this common clinical condition is of variable severity in which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. However, recent research in this area has demonstrated the importance of acinar cell death in the form of apoptosis and necrosis as a determinant of pancreatitis severity. In pancreatic cancer, various survival mechanisms have been shown to act in the prevention of cell death to result in promotion of tumor growth and metastasis. Thus, resistance of pancreatic cancer to apoptosis is the key factor preventing responses to therapies. Thus, it is for these reasons that in the current 'Primers on Molecular Pathways,' we take a closer look at the pathway cascade that is triggered during apoptosis.

摘要

细胞凋亡,即程序性细胞死亡,是一种细胞自我毁灭或细胞自杀的生理过程。该过程受促死亡信号完整性的严格调控,在多细胞生物的发育、内环境稳态维持及宿主防御中发挥关键作用。作为胰腺病学家,细胞凋亡在胰腺及其疾病状态(从糖尿病到胰腺炎再到胰腺癌)中起着核心作用。在胰腺β细胞中,凋亡性细胞死亡参与糖尿病的发病机制,因为来自死亡受体的信号和DNA损伤已被广泛认为是β细胞凋亡的触发因素。在急性胰腺炎期间,这种常见的临床病症严重程度各异,一些患者经历轻度、自限性发作,而另一些患者则表现为严重、高致死性且常致命的发作。然而,该领域的最新研究表明,腺泡细胞以凋亡和坏死形式死亡作为胰腺炎严重程度的决定因素具有重要意义。在胰腺癌中,各种存活机制已被证明可防止细胞死亡,从而促进肿瘤生长和转移。因此,胰腺癌对细胞凋亡的抵抗是阻碍治疗反应的关键因素。因此,正是出于这些原因,在当前的“分子通路引物”中,我们更深入地研究了细胞凋亡过程中触发的通路级联反应。

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