Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder

Hai Yan Wu, Kazuhito Tomizawa, Hideki Matsui

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Intracellular calcium is a powerful secondary messenger that affects a number of calcium sensors, including calpain, a Ca2+-dependent cysteine protease, and calcineurin, a Ca2+ /calmodulin-dependent protein phosphatase. Maintenance of low basal levels of intracellular calcium allows for the tightly regulated physiological activation of these proteins, which is crucial to a wide variety of cellular processes, such as fertilization, proliferation, development, learning, and memory. Deregulation of calpain and calcineurin has been implicated in the pathogenesis of several disorders, including hypertension, heart disease, diabetes, cerebral ischemia, and Alzheimer's disease. Recent studies have demonstrated an interplay between calpain and calcineurin, in which calpain can directly regulate calcineurin activity through proteolysis in glutamate-stimulated neurons in culture and in vivo. The calpain-mediated proteolytic cleavage of calcineurin increases phosphatase activity, which promotes caspase-mediated neuronal cell death. Thus, the activation of the calpain-calcineurin pathway could contribute to calcium-dependent disorders, especially those associated with Alzheimer's disease and myocardial hypertrophy. Here, we focus briefly on recent advances in revealing the structural and functional properties of these 2 calcium-activated proteins, as well as on the interplay between the 2, in an effort to understand how calpain-calcineurin signaling may relate to the pathogenesis of calcium-dependent disorders. Copyright

Original languageEnglish
Pages (from-to)123-137
Number of pages15
JournalActa Medica Okayama
Volume61
Issue number3
Publication statusPublished - Jun 2007

Fingerprint

Calpain
Calcineurin
Calcium
Alzheimer Disease
Chemical activation
Proteolysis
Deregulation
Cysteine Proteases
Phosphoprotein Phosphatases
Cell death
Calmodulin
Medical problems
Caspases
Brain Ischemia
Phosphoric Monoester Hydrolases
Fertilization
Hypertrophy
Neurons
Glutamic Acid
Heart Diseases

Keywords

  • Calcineurin
  • Calcium
  • Calpain
  • Neurodegeneration
  • Proteolysis

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Wu, H. Y., Tomizawa, K., & Matsui, H. (2007). Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder. Acta Medica Okayama, 61(3), 123-137.

Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder. / Wu, Hai Yan; Tomizawa, Kazuhito; Matsui, Hideki.

In: Acta Medica Okayama, Vol. 61, No. 3, 06.2007, p. 123-137.

Research output: Contribution to journalArticle

Wu, HY, Tomizawa, K & Matsui, H 2007, 'Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder', Acta Medica Okayama, vol. 61, no. 3, pp. 123-137.
Wu, Hai Yan ; Tomizawa, Kazuhito ; Matsui, Hideki. / Calpain-calcineurin signaling in the pathogenesis of calcium-dependent disorder. In: Acta Medica Okayama. 2007 ; Vol. 61, No. 3. pp. 123-137.
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