Figure 1530

One potential pathway in which calcium (Ca2+) and calpains play a role in renal proximal tubule cell death. These events are subsequent to mitochondrial inhibition and ATP depletion. 1) |x-Calpain releases endoplasmic reticulum (er) Ca2+ stores. 2) Release of er Ca2+ stores increases cytosolic free Ca2+ concentrations. 3) The increase in cytosolic free Ca2+ concentration mediates extracellular Ca2+ entry. (This may also occur as a direct result of er Ca2+ depletion.) 4) The influx of extracellular Ca2+ further increases cytosolic free Ca2+ concentrations. 5) This initiates the translocation of nonactivated m-calpain to the plasma membrane (6). 7) At the plasma membrane nonactivated m-calpain is autolyzed and hydrolyzes a membrane-associated substrate. 8) Either directly or indirectly, hydrolysis of the membrane-associated substrate results in influx of extracellular chloride ions (Cl-). The influx of extracellular Cl- triggers terminal cell swelling. Steps a-d represent an alternate pathway that results in extracellular Ca2+ entry. (Data from Waters et al. [12,13,14].)

0 0

Post a comment