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.
KeywordsIschemia Dementia Cysteine Luminal Glucocorticoid
Unable to display preview. Download preview PDF.
- Bellido, T., Han, L., Huening, M., Barger, S.W., Manolagas, S.C. and Christakos, S., 1998, Calbindin-D28k is expressed in osteoblastic cells and suppresses their apoptosis by inhibiting caspase 3 activity, J. Bone Min. Res. 23(Suppl. 1), S177.Google Scholar
- Christakos, S., Beck, J.D. and Hyllner, S.J., 1997, Calbindin-D28k, in Vitamin D, D. Feldman, F. Glorieux and J.W. Pike (eds.), Academic Press, San Diego, CA, pp. 209–221.Google Scholar
- Guo, Q., Sopher, B.L., Pham, D.G., Furukawa, K., Robinson, N., Martin, G.M. and Mattson, M.P., 1997, Alzheimer’s presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid ß-peptide: Involvement of calcium and oxyradicals, J. Neurosci. 17, 4212–4222.PubMedGoogle Scholar
- Keller, B.U., The role of intracellular calcium signaling in motoneuron function and disease, this book.Google Scholar
- Maki, M., Penta-EF-hand (PEF) proteins and calsenilin/DREAM: Involvement of the new EF-hand calcium-binding proteins in apoptosis and signal transduction, this book.Google Scholar
- Mattson, M.P., Chang, B., Baldwin, S., Smith-Swintosky, V.L., Keller, J., Geddes, J.V., Scheff, S.W. and Christakos, S., 1995, Brain injury and tumor necrosis factors induce calbindin-D28k in astrocytes: Evidence for a cytoprotective response, J. Neurosci. Res. 42, 357–370.PubMedCrossRefGoogle Scholar
- Mattson, M.P., Furukawa, K., Bruce, A.J., Mark, R.J. and Blanc, E.M., 1996, Calcium homeostasis and free radical metabolism as convergence points in the pathophysiology of dementia, in Molecular Mechanisms of Dementia, W. Wasco and R. E. Tanzi (eds.), Humana Press, Totowa, NJ, pp. 103–143.CrossRefGoogle Scholar
- Ono, Y., Hata, S., Sorimachi, H. and Suzuki, K., Calcium and muscle disease: Pathophysiology of calpains and limb-girdle muscular distrophy Type 2a (LGMD2A), this book.Google Scholar
- Suarez-Pinzon, W., Rabinovitch, A., Strynadka, K., Sooy, K. and Christakos, S., 1999, Cytokine mediated apoptotic destruction of pancreatic β cells, a cause of insulin dependent diabetes, is inhibited by calbindin-D28k, J. Bone Miner. Res. 14(Suppl. 1), S327.Google Scholar
- Wasserman, R.H., 1985, Nomenclature of the vitamin D induced calcium binding proteins, in Vitamin D: Chemical, Biochemical and Clinical Update, A.W. Norman, K. Schaefer, H.G. Grigoleit and D.V. Herrath (eds.), de Gruyter, Berlin, pp. 321–322.Google Scholar