THESIS
2002
xxvii, 267 leaves : ill. (some col.) ; 30 cm
Abstract
The calcium ion (Ca
2+), as an important second messenger, is known to be involved in many cellular functions. The present study is aimed at investigating the roles of Ca
2+ signaling in regulating apoptosis of mammalian cells. We tried to answer three key questions: (1) Is Ca
2+ signal involved in driving the progressing of apoptosis? (2) What are the temporal and spatial characteristics of the Ca
2+ signal in apoptosis? (3) Where and how does the Ca
2+ signal interact with the signal transduction pathway of apoptosis? By investigating the differential effects of three Ca
2+ signaling blockers (the cell-permeant free Ca
2+ chelator BAPTA/AM, the cell-impermeant BAPTA, and the IP
3 receptor antagonist heparin) on UV-induced apoptosis in HeLa cells, we have provided evidence that elevation of cy...[
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The calcium ion (Ca
2+), as an important second messenger, is known to be involved in many cellular functions. The present study is aimed at investigating the roles of Ca
2+ signaling in regulating apoptosis of mammalian cells. We tried to answer three key questions: (1) Is Ca
2+ signal involved in driving the progressing of apoptosis? (2) What are the temporal and spatial characteristics of the Ca
2+ signal in apoptosis? (3) Where and how does the Ca
2+ signal interact with the signal transduction pathway of apoptosis? By investigating the differential effects of three Ca
2+ signaling blockers (the cell-permeant free Ca
2+ chelator BAPTA/AM, the cell-impermeant BAPTA, and the IP
3 receptor antagonist heparin) on UV-induced apoptosis in HeLa cells, we have provided evidence that elevation of cytosolic Ca
2+ is indeed a part of the signal that drives the progression of apoptosis, not a result or a by-product of cell death. Using a living cell Ca
2+ imaging technique, we then characterized the cytosolic Ca
2+ changes during apoptosis induced by UV-irradiation or TNFα-treatment. An early Ca
2+ signal manifested as transient Ca
2+ increases in the cytosol was observed during the first two hours after the apoptotic treatment. This Ca
2+ event appeared to take place upstream of the key apoptotic event of cytochrome c release. A sustained Ca
2+ increase was also observed at a later stage when the apoptotic cell was undergoing morphological changes. Finally, we examined the possible components downstream of the Ca
2+ signal in UV-induced apoptosis by using specific blockers. Our results indicate that the function of the Ca
2+ signal in UV-induced apoptosis may be elicited through the Ca
2+-dependent protease calpain or the Ca
2+-dependent phosphatase calcineurin. The detailed molecular mechanisms of Ca
2+ signaling in apoptosis were discussed.
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