Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to be a hormonally active form of vitamin D3 in the regulation of intracellular and extracellular calcium levels and of differentiation of myeloid cells and epidermal keratinocytes. We found that 1 alpha,24(R)-dihydroxyvitamin D3 (1,24(OH)2D3), a novel synthetic derivative of vitamin D3, is also active in regulating the differentiation of epidermal keratinocytes. 1,24(OH)2D3 had the same affinity as 1,25(OH)2D3 for a receptor isolated from the epidermis of newborn mice. The incubation of mouse epidermal keratinocytes with 1,24(OH)2D3 induced their differentiation in a time- and dose-dependent manner, as determined by the formation of a cornified envelope and an increase in the activity of transglutaminase. 1,24(OH)2D3 inhibited DNA synthesis of epidermal keratinocytes and also increased their cytosolic calcium level. These effects of 1,24(OH)2D3 were similar to, or rather more than, those of physiologically active 1,25(OH)2D3. However, 1,24(OH)2D3 was found to cause less hypercalcemia than 1,25(OH)2D3 when administrated intravenously to rats, suggesting its possible therapeutic value in psoriasis.
 ...
PMID:1,24(R)-dihydroxyvitamin D3, a novel active form of vitamin D3 with high activity for inducing epidermal differentiation but decreased hypercalcemic activity. 216 63

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3 (1,25D), and its analogs induce normal human keratinocyte differentiation and are used for the treatment of psoriasis. Long-term topical use of 1,25D, however, causes hypercalcemia. The precursor of 1,25D, 25-hydroxyvitamin D3 (25D) is converted to 1,25D in the keratinocyte in a regulated manner. The action of 1,25D is reported to be mediated, at least in part, by cellular ceramides in the leukemia cell line, HL-60 cells. Therefore, in this study we evaluated the synergy between 25D and short chain cell permeable ceramides (SCC) or synthetic analogs of ceramides on keratinocyte growth and differentiation in vitro. C2 ceramide (acetyl sphingosine) synergistically enhanced the growth inhibitory effect of 25D and 1,25D in a concentration-dependent manner. Short chain analogs of ceramide-like compounds, neoceramides and pseudoceramides, also inhibited keratinocyte proliferation and acted in synergy with 25D and 1,25D. SCC alone increased transglutaminase and cornified envelope levels. 25D potentiated this prodifferentiating effect of SCC. Twenty-four-hour preincubation with SCC did not alter 25D or 1,25D uptake into keratinocytes. These studies demonstrate a synergy between vitamin D metabolites and ceramides in human keratinocytes and indicate the potential of using 25D as an effective and safer alternative to deliver 1,25D benefits to the epidermis.
 ...
PMID:Synergy between vitamin D precursor 25-hydroxyvitamin D and short chain ceramides on keratinocyte proliferation and differentiation. 962 90