Apoptosis in Renal damage

[shalmoli]

Cells can die by two distinct pathwaysi.e either by 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. 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 which is a hallmark of apoptosis. 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. 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.

[admin]

Excellent post Shalmoli!

thank you for the great information

[beyondxiao]

there is a new type of cell death----necroptosis, which was dicovered by Junying Yuan.
A new pathway to necrosis, a form of cell death, is described in July's Nature Chemical Biology. Necrosis is a common feature of human pathologies from stroke to neurodegeneration and unlike apoptosis -- a precisely orchestrated cellular pathway to initiate death -- was generally believed to be a passive cellular response to external damage. Junying Yuan and colleagues identify a previously unknown cellular pathway leading to necrosis, which they call necroptosis. The team demonstrate its involvement in conditions where not enough blood reaches the brain -- otherwise known as ischemic brain injury.

A growing number of studies have reported evidence for non-apoptotic cell death with some features of necrosis. However, scientists have had no tools to investigate the potential mechanisms behind these observations. To address this, Yuan and colleagues identified a chemical, necrostatin-1, which specifically inhibited this non-apoptotic cell death. They found that necrostatin-1 blocked all cases of this cell death, demonstrating the existence of a specific cellular pathway, necroptosis, leading to necrosis. They further showed that necrostatin-1 reduced ischemic brain injury in a mouse model of stroke, establishing a causal role of necroptosis in ischemic trauma-induced neuronal damage. Necrostatin-1 is a promising therapeutic lead for treating patients with brain injury following stroke.

In addition to its therapeutic potential, necrostatin-1 provides an important new chemical tool for investigating the precise molecular mechanism of necroptosis and the role of this pathway in other pathologies involving necrosis.