title: High energy phosphates, phospholipids, and calcium in ischemic renal tubular cell injury.
abstract: Substantial data is available supporting critical roles for high energy phosphates, calcium, and phospholipids in ischemic cell injury. Although it has been proposed that one of these compounds may be most critical and defines the "final common pathway" for lethal cell injury, it is more accurate to define the pathogenesis of ischemic cell injury as the simultaneous derangement of several critical metabolic process which act in concert to produce a cascade of events that finally lead to plasma and subcellular membrane dysfunction incompatible with the maintenance of cell viability and integrity. As detailed in Figure 1, a tentative scheme is proposed interrelating high energy phosphate depletion, cellular calcium derangements, and membrane phospholipid degradation and loss. Ischemia directly leads to declines in the rate of oxidative phosphorylation due to a lack of oxygen availability. A fall in cellular ATP levels develops. Ischemia also promotes a redistribution of intracellular calcium pools and results in phospholipase activation and phospholipid degradation. When phospholipid degradation occurs concomitantly with a decline in high energy phosphate levels, phospholipid synthesis cannot keep pace with phospholipid degradation and net membrane phospholipid loss occurs. An increase in plasma membrane calcium permeability develops and the influx of calcium down its electrochemical gradient from extracellular to intracellular spaces occurs. This calcium is taken up and sequestered in mitochondria and causes further alterations in mitochondrial structure and function, leading to further declines in cellular ATP content.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology; D000255:Adenosine Triphosphate / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D007511:Ischemia / Q000378:metabolism*; D007683:Kidney Tubular Necrosis, Acute / Q000209:etiology; D007684:Kidney Tubules / Q000098:blood supply* / Q000378:metabolism; D010085:Oxidative Phosphorylation; D010710:Phosphates / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*
chemical_list: D010710:Phosphates; D010743:Phospholipids; D000255:Adenosine Triphosphate; D002118:Calcium