Chang Wilson J, Chehab Monzer, Kink Shaun, Toledo-Pereyra Luis H
Kalamazoo Center for Medical Studies, Michigan State University, Kalamazoo, Michigan, USA.
J Invest Surg. 2010 Aug;23(4):228-38. doi: 10.3109/08941939.2010.496036.
Calcium plays a major role in intracellular signaling mechanisms during ischemia reperfusion (I/R) injury of a liver cell. Under ischemic conditions, the absence of oxygen arrests oxidative phosphorylation, thereby eliminating the energy source by which hepatocellular mechanisms maintain homeostasis of calcium. This, in turn, leaves nonselective plasma membrane influx pores unopposed and results in a net increase in intracellular calcium concentrations. Subsequent reperfusion marks the onset and progression of apoptosis and necrosis, as it involves inflammatory responses as well as free-radical formation due to re-oxygenation of cells. These processes destroy the structural integrity of organelles, leading to disruptive redistribution of calcium between cellular and subcellular compartments. This initial elevation and later imbalance of intracellular calcium concentrations associated with I/R induce various molecular responses within each organelle. In the cytoplasm, a series of pro-apoptotic pathways involving various calcium sensitive enzymes are activated. The injury is further exacerbated in the endoplasmic reticulum (ER) due to the malfunction of mechanisms responsible for intracellular calcium sequestration. Both the mitochondria and the nucleus are also adversely affected, as their structural integrity and physiologic functions are disrupted. To date, however, the precise pathophysiology of these calcium-mediated signaling pathways is not fully understood due to its complex nature. This review aims to systematically examine the current literature about individual molecular signaling pathways in the cytoplasm, ER, mitochondria, and the nucleus prior to causing time-sensitive progression of permanent tissue injury.
钙在肝细胞缺血再灌注（I/R）损伤期间的细胞内信号传导机制中起主要作用。在缺血条件下，缺氧会使氧化磷酸化停止，从而消除肝细胞维持钙稳态的能量来源。这反过来又使非选择性质膜流入孔不受阻碍，导致细胞内钙浓度净增加。随后的再灌注标志着细胞凋亡和坏死的开始和进展，因为它涉及炎症反应以及由于细胞再氧合而产生的自由基形成。这些过程破坏了细胞器的结构完整性，导致钙在细胞和亚细胞区室之间的破坏性重新分布。与I/R相关的细胞内钙浓度的最初升高和随后的失衡在每个细胞器内引发各种分子反应。在细胞质中，一系列涉及各种钙敏感酶的促凋亡途径被激活。由于负责细胞内钙螯合的机制失灵，内质网（ER）中的损伤进一步加剧。线粒体和细胞核也受到不利影响，因为它们的结构完整性和生理功能被破坏。然而，由于其性质复杂，这些钙介导的信号通路的确切病理生理学至今尚未完全了解。本综述旨在系统地研究目前关于细胞质、内质网、线粒体和细胞核中单个分子信号通路的文献，这些通路在导致永久性组织损伤的时间敏感进展之前。
