Nongenomic Activities of Vitamin D
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 (cal...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/14/23/5104 |
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| author | Michał A. Żmijewski |
| author_facet | Michał A. Żmijewski |
| author_sort | Michał A. Żmijewski |
| collection | DOAJ |
| description | 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)<sub>2</sub>D<sub>3</sub>) 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. |
| first_indexed | 2024-03-09T17:37:17Z |
| format | Article |
| id | doaj.art-f073c17cecb1404ab96244302ba9818f |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-09T17:37:17Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-f073c17cecb1404ab96244302ba9818f2023-11-24T11:52:13ZengMDPI AGNutrients2072-66432022-12-011423510410.3390/nu14235104Nongenomic Activities of Vitamin DMichał A. Żmijewski0Department of Histology, Faculty of Medicine, Medical University of Gdańsk, PL-80211 Gdańsk, PolandVitamin 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)<sub>2</sub>D<sub>3</sub>) 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.https://www.mdpi.com/2072-6643/14/23/5104vitamin DVDRnongenomic responsePDIA3ultraviolet radiationmegalin |
| spellingShingle | Michał A. Żmijewski Nongenomic Activities of Vitamin D Nutrients vitamin D VDR nongenomic response PDIA3 ultraviolet radiation megalin |
| title | Nongenomic Activities of Vitamin D |
| title_full | Nongenomic Activities of Vitamin D |
| title_fullStr | Nongenomic Activities of Vitamin D |
| title_full_unstemmed | Nongenomic Activities of Vitamin D |
| title_short | Nongenomic Activities of Vitamin D |
| title_sort | nongenomic activities of vitamin d |
| topic | vitamin D VDR nongenomic response PDIA3 ultraviolet radiation megalin |
| url | https://www.mdpi.com/2072-6643/14/23/5104 |
| work_keys_str_mv | AT michałazmijewski nongenomicactivitiesofvitamind |