Role of apoptosis of renal tubular cells in acute renal failure: therapeutic implications.
Acute renal failure (ARF) can be defined as a sudden loss of renal function and is a common and serious clinical problem. There are many causes of ARF but the most common cause results from injury to the renal tubular epithelial cells (RTECs). RTECs can be injured by schemia or by cytotoxic agents and, once injured, can die by necrosis or apotosis. In general, necrosis occurs in response to any severe injury, which leads to the biochemical collapse of the cell. Milder forms of the same types of injury cause apoptosis. At the cellular level there are fundamental differences between necrosis and apoptosis. Necrosis results from the additive effect of a number of independent biochemical events that are activated by severe depletion of cell energy stores. By contrast, apoptosis occurs via a coordinated, predictable and pre-determined pathway. These biochemical differences between apoptosis and necrosis have important therapeutic implications. Once a cell has been severely injured, necrosis is difficult to prevent. By contrast, the apoptotic pathway can potentially be modulated to maintain cell viability. The components of the apoptotic pathway that are potentially amenable to therapeutic modulation are discussed in detail in this review.
Rana
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Diabetes Research Unit, Massachusetts General Hospital, Harvard Medical School, Boston, USA. arana@medicine.tamu.edu
Sathyanarayana
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P
Lieberthal
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W
D058186:Acute Kidney Injury / Q000188:drug therapy / Q000473:pathology*; D017209:Apoptosis / Q000187:drug effects; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects