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 Ca2+ signaling. Oxidative stress causes Ca2+ 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 Ca2+ concentration in the cytoplasm causes Ca2+ influx into mitochondria and nuclei. In mitochondria Ca2+ accelerates and disrupts normal metabolism leading to cell death. In nuclei Ca2+ modulates gene transcription and nucleases that control cell apoptosis. Both in nuclei and cytoplasm Ca2+ 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 Ca2+ signaling can help to understand process of aging and disease, and may lead to new strategies for their prevention. [Copyright &y& Elsevier]