Vitamin D cell signalling in health and disease

Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation

“…The first module that changed with vitamin D supplementation contained metabolites involved in redox homeostasis: glutathione metabolism and protein oxidation. This is consistent with current knowledge about the molecular effects of vitamin D on related pathways, such as the Nrf2 antioxidant pathway, which leads to activation of the glutathione-S-transferase A2 enzyme, and the antiaging protein Klotho (27,28). This is also consistent with the relationship between vitamin D deficiency and elevated markers of oxidative stress and the reduction of markers of oxidative stress with vitamin D supplementation in multiple populations (12,13,29).…”

Vitamin D, reactive oxygen species and calcium signalling in ageing and disease

“…Most individuals who develop these diseases are completely unaware that the disease is developing, and it is this aspect that may be explained by the subtle modulatory activity of the InsP 3 /Ca 2þ signalling pathway. It will be argued that one of the main causes of the alteration in this modulatory pathway is vitamin D deficiency that causes the small alterations in the Ca 2þ signalling pathway responsible for the onset of these two diseases [1][2][3]. All this evidence raises a major question concerning what it is about vitamin D that makes it such an important component of a healthy life.…”

“…Any hypothesis as to how vitamin D deficiency might contribute to disease has to take into account a possible relationship between ageing and vitamin D deficiency. There is increasing evidence that vitamin D acts by maintaining the integrity of cell signalling pathways such as those regulated by Ca 2þ and reactive oxygen species (ROS) [1][2][3]. It will be argued that low vitamin D levels result in an increase in the activity of these two signalling pathways that not only act to accelerate the ageing process but may also set the stage for the onset of a large number of diseases.…”

Vitamin D in Oxidative Stress and Diseases

“…In a recent study, Berridge suggests the idea that vitamin D plays a crucial activity in keeping the integrity of cell signaling pathways coining the term of "custodian of phenotypic stability" [19]. The hypothesis supported is that a loss of this integrity could be explained by vitamin D deficiency, and this represents a risk factor for different diseases.…”

“…The hypothesis supported is that a loss of this integrity could be explained by vitamin D deficiency, and this represents a risk factor for different diseases. This role assigned to vitamin D may depend on the regulation of the expression of nuclear factors involved both in physiological control of ROS and in calcium signaling [19]. The hormonally active form of vitamin D, 1α25(OH)2D 3 , influences the expression of various genes, whose products not only are involved in the control of calcium and phosphate homeostasis, but are also able to interact with a wide range of organs and target tissues different from those involved in calcium metabolism [20].…”