Evolutionary Biology and Pathology of Vitamin D

Holick, Michael F.

doi:10.3177/jnsv.38.special_79

Cited by 21 publications

(14 citation statements)

References 16 publications

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“…Vitamin D is produced by both single-cell plants and animals (Holick 1992); DBP is the most primitive of all the albuminoid proteins (Fasano et al 2007) and an ancestral VDR first appears in nematodes (Carosa et al 1998). These observations provide an invaluable platform for better understanding the role of vitamin D in modern human physiology.…”

Section: Discussionmentioning

confidence: 99%

“…NWPs are also profoundly resistant to vitamin D. As with glucocorticoids, this appears to be due to impaired signaling via the cognate intracellular receptor, in this case the VDR. Initial studies suggested that the blockade of VDR action in NWPs was due to the elevated levels of a soluble protein that could act as a competitor for binding of 1,25(OH) 2 D (Gacad & Adams 1991, 1992. The purification of this intracellular DBP (IDBP) revealed similarity to the constitutively expressed human heat-shock protein 70 (hsc70) , and also indicated that hsc70 was capable of binding both 25OHD and 1,25(OH) 2 D, as well as gonadal steroids such as estradiol ).…”

Section: Primate Responses To Vitamin D Metabolites: New World Versusmentioning

confidence: 99%

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Back to the future: a new look at ‘old’ vitamin D

Chun¹,

Adams²,

Hewison³

2008

Journal of Endocrinology

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Our perception of the vitamin D system continues to evolve. Recent studies have re-evaluated the parameters for adequate vitamin D status in humans, revealing a high prevalence of insufficiency in many populations throughout the world. Other reports have highlighted the potential consequences of vitamin D insufficiency beyond established effects on bone homeostasis. Most notably, there is now strong evidence of a role for vitamin D in modulating innate and adaptive immunities, with insufficiency being linked to infectious disease and other immune disorders. To date, signaling pathways for these new responses to vitamin D have been based on established endocrine models for active 1,25-dihydroxyvitamin D, despite present evidence for more localized, intracrine modes of action. In the following review, we provide a fresh perspective on vitamin D signaling in nonclassical target cells such as macrophages by highlighting novel factors associated with the transport and action of this pluripotent secosteroid.

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Section: Discussionmentioning

confidence: 99%

Section: Primate Responses To Vitamin D Metabolites: New World Versusmentioning

confidence: 99%

Back to the future: a new look at ‘old’ vitamin D

Chun¹,

Adams²,

Hewison³

2008

Journal of Endocrinology

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“…The actions of calcitriol in calcium homeostasis, control of cell growth and differentiation, cell adhesion, and apoptosis (controlled cell death) are mediated by its interaction with the vitamin D receptor (VDR), a member of the nuclear receptor superfamily 61 ( Figure 2). Vitamin D receptors are present in many cell types including heart, muscle, breast, colon, prostate, brain, kidney, bone, intestine, osteoblasts, and immune cells 60,62 . Upon entry into a cell's cytoplasm, calcitriol binds to its nuclear receptor and recruits specific molecules to form active complexes that translocate to the nucleus and subsequently bind to vitamin D response elements (VDREs) in the promoters of vitamin-D responsive target genes.…”

Section: Vitamin D Sources and Regulatory Processesmentioning

confidence: 99%

Molecular basis of the potential of vitamin D to prevent cancer

2008

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Research strongly supports the view that efforts to improve vitamin D status would have significant protective effects against the development of cancer. The clinical research community is currently revising recommendations for optimal serum levels and for sensible levels of sun exposure, to levels greater than previously thought. Currently, most experts in the field believe that intakes of between 1000 and 4000 IU will lead to a more healthy level of serum 25(OH)D, at approximately 75 nmol/L that will offer significant protection effects against cancers of the breast, colon, prostate, ovary, lungs, and pancreas. The first randomized trial has shown significant protection against breast cancer, and other clinical trials will follow and ultimately lead to improved public health policies and significantly fewer cancers.

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“…Following the discovery of the vitamin D receptor (VDR), which is expressed in a wide range of tissues, the role of vitamin D in the prevention and treatment of chronic diseases has become an important area of study (Holick, 1992; Kalueff and Tuohimaa, 2007). Vitamin D deficiency has been linked to various health problems, including cognitive decline, depression, cardiovascular disease, hypertension, type 2 diabetes, and cancer (Butler et al, 2011; Chan, 2011; Holick, 2003; Ingraham et al, 2008; Ito et al, 2011; Liu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1

et al. 2016

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Summary Vitamin D has multiple roles including the regulation of bone and calcium homeostasis. Deficiency of 25-hydroxyvitamin D, the major circulating form of vitamin D, is associated with an increased risk of age-related chronic diseases including Alzheimer’s disease, Parkinson’s disease, cognitive impairment, and cancer. In this study, we utilized Caenorhabditis elegans to examine the mechanism by which vitamin D influences aging. We found that Vitamin D3-induced lifespan extension requires the stress response pathway genes SKN-1, IRE-1, and XBP-1. Vitamin D3 (D3) induced expression of SKN-1 target genes, but not canonical targets of IRE-1/XBP-1. D3 suppressed an important molecular pathology of aging, that of widespread protein insolubility, and prevented toxicity caused by human β-amyloid. Our observation that D3 improves protein homeostasis and slows aging highlights the importance of maintaining appropriate vitamin D serum levels, and may explain why such a wide variety of human age-related diseases are associated with vitamin D deficiency.

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Evolutionary Biology and Pathology of Vitamin D

Cited by 21 publications

References 16 publications

Back to the future: a new look at ‘old’ vitamin D

Back to the future: a new look at ‘old’ vitamin D

Molecular basis of the potential of vitamin D to prevent cancer

Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1

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