Calcium and oxidative stress: from cell signaling to cell death

Mol Immunol. 2002 Feb;38(10):713-21. doi: 10.1016/s0161-5890(01)00108-0.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Calcium / physiology*
  • Calcium Signaling / physiology
  • Cell Death / physiology
  • Humans
  • Oxidative Stress / physiology*
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / physiology


  • Reactive Nitrogen Species
  • Reactive Oxygen Species
  • Calcium