Activation of Programmed Cell Death by Calcium: Protection against Cell Death by the Calcium Binding Protein, Calbindin-D28k
Calcium has been known to be a potent second messenger for a wide range of cellular processes from fertilization to cell death. It has been implicated in the regulation of protein kinases, phosphatases, protease activity, chromatin structure and transcription as well as in the regulation of muscle contraction, nerve transmission, cytoskeletal organization, cell cycle progression and differentiation (Berridge, 1997; Berridge et al., 1998). Calcium homeostasis is tightly regulated such that any exogenous or internally generated calcium load is rapidly controlled to maintain calcium balance. Calcium ions signal from outside to inside by raising the intracellular cytosolic calcium concentration. An increase in cytosolic calcium can also occur inside the cell by release from stores. The mitochondria and the endoplasmic reticulum cross talk with each other to modulate the cytosolic calcium concentration. Thus an interplay among membrane components, intracellular organelles, calcium pumps and ion channels exists. Although calcium signaling is complex and incorporates multiple factors, it has been suggested that the ability of the calcium ion to interact with a family of calcium binding proteins (Kd = 10−8–10−10 M), known as EF-hand proteins, can play an important role in the transduction of the calcium signal into a biological response (Christakos et al., 1989, 1997; Heizmann and Braun, 1992; Heizmann and Hunziker, 1991; Schafer and Heizmann, 1996; Zimmer et al., 1995). This family of calcium binding proteins consists of over 200 members and is characterized by the EF-hand structural motif.
KeywordsPC12 Cell Calcium Binding Protein Temporal Lobe Epilepsy Patient Dentate Granule Cell Cytosolic Calcium Concentration
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