TRAIL death receptors, Bcl-2 protein family, and endoplasmic reticulum calcium pool.
Calcium (Ca(2+)) is one of the highly versatile second messengers critical in cellular pathophysiology. Alterations in Ca(2+) homeostasis affect many cellular processes, including apoptosis. Recent studies have started to unravel the molecular mechanisms of apoptosis regulation in context to intracellular Ca(2+) pools. In this regard, Bcl-2 has been reported to mediate its anti-apoptotic effects, partly, by lowering the endoplasmic reticulum (ER) Ca(2+) load and by inhibiting the mitochondrial uptake of Ca(2+). However, the opposite is true for Bax and Bak that promote apoptosis, in part, by increasing the ER Ca(2+) load and Ca(2+) transfer from the ER to mitochondria. Massive ER Ca(2+) depletion coupled with upregulation of DR5 has also been reported to induce apoptosis. The mechanistic details of how some of these molecules affect intracellular Ca(2+) contents and sense perturbations in Ca(2+) homeostasis remain to be elucidated. The recent explosion of information in the fields of cell signaling and apoptosis is likely to facilitate the future investigations aiming to explore these issues.
Sheikh
M Saeed
MS
Department of Pharmacology State University of New York Upstate Medical University Syracuse, New York 13210, USA.
Huang
Ying
Y
D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D004265:DNA Helicases / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D029968:Escherichia coli Proteins; D006706:Homeostasis; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology*; D015398:Signal Transduction
D029968:Escherichia coli Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018124:Receptors, Tumor Necrosis Factor; C027093:TraI protein, E coli; D004265:DNA Helicases; D002118:Calcium