Calcium and oxidative stress: from cell signaling to cell death.
Reactive oxygen and nitrogen species can be used as a messengers in normal cell functions. However, at oxidative stress levels they can disrupt normal physiological pathways and cause cell death. Such a switch is largely mediated through Ca(2+) signaling. Oxidative stress causes Ca(2+) influx into the cytoplasm from the extracellular environment and from the endoplasmic reticulum or sarcoplasmic reticulum (ER/SR) through the cell membrane and the ER/SR channels, respectively. Rising Ca(2+) concentration in the cytoplasm causes Ca(2+) influx into mitochondria and nuclei. In mitochondria Ca(2+) accelerates and disrupts normal metabolism leading to cell death. In nuclei Ca(2+) modulates gene transcription and nucleases that control cell apoptosis. Both in nuclei and cytoplasm Ca(2+) can regulate phosphorylation/dephosphorylation of proteins and can modulate signal transduction pathways as a result. Since oxidative stress is associated with many diseases and the aging process, understanding how oxidants alter Ca(2+) signaling can help to understand process of aging and disease, and may lead to new strategies for their prevention.
Ermak
Gennady
G
Ethel Percy Andrus Gerontology Center, and Division of Molecular Biology, University of Southern California, Rm 306, 3715 McClintock Avenue, Los Angeles, CA 90089-0191, USA.
Davies
Kelvin J A
KJ
D000818:Animals; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology; D016923:Cell Death / Q000502:physiology; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology*; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D002118:Calcium