The alveolar macrophage as a model of calcium signaling in oxidative stress.
Regulation of the free intracellular calcium concentration, [Ca2+]i, plays a major role in physiological signal transduction. Many of the essential enzymes in signaling cascades are Ca(2+)-dependent, as are numerous proteins that participate in the regulated function. Oxidative stress, which for many years was considered synonymous with cell and tissue injury, has more recently been demonstrated to alter signal transduction in both positive and negative directions. The realization that hydrogen peroxide and lipid hydroperoxides are produced as part of normal metabolism has led to the proposal that these oxidants function as second messengers. Exposure to environmental and other agents that produce hydroperoxides or the addition of exogenous hydroperoxides also causes elevation of [Ca2+]i in some cells. At sublethal exposure to hydroperoxides, the elevation in [Ca2+]i can either alter or mimic physiological stimulation. In addition to endoplasmic reticulum, mitochondria, and the extracellular space, the phospholipid- and Ca(2+)-binding proteins known as annexins constitute a Ca2+ pool from which this ion may be released under situations of oxidative stress. In this article, the source and consequences of Ca2+ elevation are reviewed with an emphasis on studies done with alveolar macrophages. These phagocytes, which modulate much of the physiological and immunological function of the lung, are susceptible targets for environmental oxidants.
Hoyal
C R
CR
Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033, USA.
Girón-Calle
J
J
Forman
H J
HJ
D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004781:Environmental Exposure; D006801:Humans; D015227:Lipid Peroxidation; D016676:Macrophages, Alveolar / Q000502:physiology*; D018384:Oxidative Stress; D015398:Signal Transduction
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D002118:Calcium