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Vitamin D interacts with more than genes (mitochondria, etc) – Dec 2022

Nongenomic Activities of Vitamin D

Nutrients 2022, 14(23), 5104; https://doi.org/10.3390/nu14235104
Michał A. Żmijewski Department of Histology, Faculty of Medicine, Medical University of Gdańsk, PL-80211 Gdańsk, Poland

Pathways
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PDF Contents
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Vitamin D shows a variety of pleiotropic activities which cannot be fully explained by the stimulation of classic pathway- and vitamin D receptor (VDR)-dependent transcriptional modulation. Thus, existence of rapid and nongenomic responses to vitamin D was suggested. An active form of vitamin D (calcitriol, 1,25(OH)2D3) is an essential regulator of calcium–phosphate homeostasis, and this process is tightly regulated by VDR genomic activity. However, it seems that early in evolution, the production of secosteroids (vitamin-D-like steroids) and their subsequent photodegradation served as a protective mechanism against ultraviolet radiation and oxidative stress. Consequently, direct cell-protective activities of vitamin D were proven. Furthermore, calcitriol triggers rapid calcium influx through epithelia and its uptake by a variety of cells. Subsequently, protein disulfide-isomerase A3 (PDIA3) was described as a membrane vitamin D receptor responsible for rapid nongenomic responses.

Vitamin D was also found to stimulate a release of secondary massagers and modulate several intracellular processes—including cell cycle, proliferation, or immune responses—through wingless (WNT), sonic hedgehog (SSH), STAT1-3, or NF-kappaB pathways.

Megalin and its coreceptor, cubilin, facilitate the import of vitamin D complex with vitamin-D-binding protein (DBP), and its involvement in rapid membrane responses was suggested.

Vitamin D also directly and indirectly influences mitochondrial function, including

  • fusion–fission,
  • energy production,
  • mitochondrial membrane potential,
  • activity of ion channels, and
  • apoptosis.

Although mechanisms of the nongenomic responses to vitamin D are still not fully understood, in this review, their impact on physiology, pathology, and potential clinical applications will be discussed.
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VitaminDWiki - Vitamin D actions which are faster than gene interactions – March 2016

The Non-Genomic Actions of Vitamin D
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Vitamin D interacts with more than genes (mitochondria, etc) – Dec 2022        
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