Lieberthal W, Levine J S
Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, Massachusetts 02118, USA.
Am J Physiol. 1996 Sep;271(3 Pt 2):F477-88. doi: 10.1152/ajprenal.1996.271.3.F477.
Cells can die by two distinct pathways: apoptosis or necrosis. Necrosis is associated with rapid metabolic collapse that leads to cell swelling, early loss of plasma membrane integrity, and ultimate cell rupture. Cytosolic contents leak from the necrotic cell causing injury and inflammation to surrounding tissue. In contrast, apoptosis is an energy-requiring, gene-directed process, which, when activated, results in cell "suicide." The morphological and biochemical characteristics of cells dying by apoptosis differ markedly from those of cells dying by necrosis. During apoptosis, cells decrease in size and round up. The nuclear chromatin undergoes condensation and fragmentation. The apoptotic cell then breaks apart into many plasma membrane-bound vesicles called "apoptotic bodies," which contain fragments of condensed chromatin and morphologically intact organelles such as mitochondria. Apoptotic cells and bodies are rapidly phagocytosed, thereby protecting surrounding tissues from injury. The rapid and efficient clearance of apoptotic cells makes apoptosis extremely difficult to detect in tissue sections. Recent studies show that multiple cytotoxic stimuli well known to cause necrosis can lead to apoptosis instead when cells are exposed to the same noxious agents at lower concentrations. This insight has led to an interest in the role of apoptosis in the pathogenesis of renal diseases that result primarily from injury to renal tubular epithelial cells. These diseases include acute and chronic renal failure from exposure of the kidney to ischemia or to cytotoxic agents. In this review we discuss some relevant aspects of the differences between necrotic and apoptotic cell death. We also present evidence to support the hypothesis that apoptosis is an important pathogenic mechanism in those forms of acute and chronic renal failure in which the renal tubular epithelial cell is the primary target of ischemic or toxic injury.
凋亡或坏死。坏死与快速的代谢崩溃相关，会导致细胞肿胀、质膜完整性早期丧失以及最终细胞破裂。胞质内容物从坏死细胞中泄漏，对周围组织造成损伤和炎症。相比之下，凋亡是一个需要能量的、由基因指导的过程，激活后会导致细胞“自杀”。通过凋亡死亡的细胞的形态和生化特征与通过坏死死亡的细胞明显不同。在凋亡过程中，细胞体积减小并变圆。核染色质发生浓缩和碎片化。然后凋亡细胞分裂成许多被质膜包裹的囊泡，称为“凋亡小体”，其中包含浓缩染色质片段和形态完整的细胞器，如线粒体。凋亡细胞和凋亡小体迅速被吞噬，从而保护周围组织免受损伤。凋亡细胞的快速有效清除使得在组织切片中极难检测到凋亡。最近的研究表明，当细胞暴露于较低浓度的相同有害剂时，多种已知会导致坏死的细胞毒性刺激反而会导致凋亡。这一见解引发了人们对凋亡在主要由肾小管上皮细胞损伤引起的肾脏疾病发病机制中的作用的兴趣。这些疾病包括因肾脏暴露于缺血或细胞毒性剂而导致的急性和慢性肾衰竭。在本综述中，我们讨论了坏死性和凋亡性细胞死亡之间差异的一些相关方面。我们还提供证据支持以下假设：在那些以肾小管上皮细胞为缺血或毒性损伤主要靶点的急性和慢性肾衰竭形式中，凋亡是一种重要的致病机制。
