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Calcium-mediated silica cytotoxicity.

Authors
Rojanasakul-Y; Castranova-V; Banks-DE; Ma-JKH
Source
Silica and Silica-Induced Lung Diseases. Castranova V, Vallyathan V, Wallace WE, eds., Boca Raton, FL: CRC Press, 1995 Dec; :151-161
Link
NIOSHTIC No.
20037001
Abstract
There is evidence that cytotoxic injury that occurs following phagocytic activation of alveolar macrophages (AMs) by silica particles may be caused by the alteration of intracellular calcium [Ca2+}, homeostasis, as well as the generation of reactive oxygen radicals (ORs). Until recently, however, the relationship between these two mechanisms of injury has not been directly addressed. In the case of reactive oxygen species, there is almost universal agreement that oxygen radicals can cause lipid peroxidation of unsaturated fatty acids within membranes leading to disruption of membrane functions and destruction of cells. As for calcium, the perturbation of its cellular control mechanisms, which leads to sustained accumulation of [Ca2+] has long been recognized as the major determinative factor leading to irreversible cell injury. Several recent studies have indicated that silica can induce a rise in [Ca2+] as well as the generation of ORs, and that the inhibition of these cellular processes by calcium chelators or OR scavengers can prevent cell death. The perturbation of [Ca2+], homeostasis by silica has been shown to activate several degradative enzymes such as phospholipases, proteases, and endonucleases and cause disruptions of cytoskeletal and other structural proteins. The present report will review existing evidence for the involvement of calcium in these cellular processes and its relationship to ORs in silica toxicity. Attempts will also be made to elucidate potential mechanisms involved in these cytotoxic processes.
Keywords
Silicates; Humans; Occupational-hazards; Pulmonary-system-disorders; Lung-disorders; Free-radicals; Free-radical-generation; Antioxidants; Antioxidation
CAS No.
14808-60-7
Publication Date
19951220
Document Type
Book or book chapter
Editors
Castranova-V; Vallyathan-V; Wallace-WE
Fiscal Year
1996
NTIS Accession No.
NTIS Price
ISBN No.
0849347092
NIOSH Division
DRDS
Source Name
Silica and Silica-Induced Lung Diseases
State
WV
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