Inositol 1,4,5-triphosphate calcium release from endoplasmic

There is evidence for immunosuppressive effects of PAHs in rodents (Davila et al. 1997). For example, strong immunosuppressive effects were reported in mice that had been dosed with benzo[fl]pyrene and 3-methyl cholanthrene, effects that persisted for up to 18 months (Environmental Health Criteria 202). Multiple immu-notoxic effects have been reported in rodents, and there is evidence that these result from disturbance of calcium homeostasis (Davila et al. 1997). PAHs can activate protein tyrosine kinases in T cells that initiate the activation of a form of phospholipase C. Consequently, release of inositol triphosphate—a molecule that immobilizes Ca + from storage pools in the endoplasmic reticulum—is enhanced. 

There is a delicate balance between cellular membrane permeability and intracellular calcium homeostasis during CVB3 infection. It has been well-documented that sustained elevation of calcium levels in the cytosol precedes Cyt c release from the mitochondria, and that the small amount of released Cyt c interacts with the inositol triphosphate receptor (IP3R) on the endoplasmic reticulum (ER) and prevents inhibition of ER calcium release. The overall increase of calcium leads to a massive release of Cyt c to maintain ER calcium release through interaction with the IP3Rs in a positive feedback loop, and to activate downstream caspases to execute apoptosis of damaged cells. 

Neuronal and hormonal signals may often be transduced via receptor-mediated activation of phophoinositidase C (inositol lipid-directed phospholipase C), which converts phosphatidyl-inositol 4,5-bisphosphate (PIP2) to 1,2-diacyl-glycerol (1,2 DG) and D-inositol 1,4,5-triphosphate [(1,4,5)IP3] in the cell membrane. These metabolic products are second messengers 1,2 DG stimulates protein kinase C and (1,4,5)IP3 releases intracellular calcium from the endoplasmic reticulum. Subsequently, (1,4,5)IP3 is ultimately converted to myoinositol. That in turn is converted to phosphatidylinositol, which is used to replenish PIP2 stores and thus complete the cycle. ... 

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