Novel regulatory actions of 1α,25‐dihydroxyvitamin D₃ on the metabolism of polyphosphoinositides in murine epidermal keratinocytes

Abstract

The in vitro incubation of murine keratinocytes in the presence of 1 alpha,25-dihydroxyvitamin D3 enhanced the rapid hydrolysis of the prelabeled keratinocyte polyphosphoinositides (polyPtdIns) when compared to untreated cells. The rapid hydrolysis of the polyPtdIns and the release of the inositol phosphates (particularly InsP3 and InsP2) precede the onset of differentiation of these cells. These data therefore suggest that 1 alpha,25-dihydroxyvitamin D3 functions in vitro to initiate the rapid generation of InsP3 from cellular polyPtdIns; this in turn may mobilize intracellular Ca2+, thus providing the signal which program the murine keratinocytes from a proliferating mode into a differentiating mode.

Nongenomic Steroid Action: Controversies, Questions, and Answers

“…Rapid actions on Ca 2ϩ fluxes in bone-forming osteoblasts which function as an integral part of the vitamin D endocrine system and are main target cells for 1␣,25(OH) 2 (102), and keratinocytes (476), but also in cells like primary chick-embryo muscle cells (315) and hepatocytes (23). In rat skeletal muscle, the involvement of PLC and a PTX-sensitive G protein in the rapid 1␣,25(OH) 2 D 3 -induced release of IP 3 /inositol phosphates and DAG has been shown (137,314).…”

1,25-Dihydroxyvitamin D3 upregulates the phosphatidylinositol signaling pathway in human keratinocytes by increasing phospholipase C levels.

“…In keratinocytes, an acute increase in Cai associated with increased PI turnover has been observed after 1,25 (OH)2D3 administration in some studies (17)(18)(19)(20). The acute increase in Cai in association with the increased levels of diacylglycerol produced from the PI turnover would be expected to activate protein kinase C (26,27 (28,29).…”

Hybrid structural analogues of 1,25-(OH)2D3 regulate chondrocyte proliferation and proteoglycan production as well as protein kinase C through a nongenomic pathway

“…More recently, a second pathway has emerged, involving rapid membrane events generally associated with peptide hormone stimulation of transmembrane receptors [Norman and Collins, 1996]. 1,25-(OH) 2 D 3 and 24,25-(OH) 2 D 3 have been shown to act directly on the plasma membrane of target cells, causing rapid changes in calcium flux Zhou et al, 1992;Langston et al, 1990;Farach-Carson et al, 1991], fatty acid metabolism Swain et al, 1992;Matsumoto et al, 1981;Rasmussen et al, 1982], phospholipid metabolism [Bourdeau et al, 1990;Tang et al, 1987;Wali et al, 1990;Lieberherr et al, 1989], membrane fluidity [Swain et al, 1993], and protein kinase C (PKC) activity [Sylvia et al, 1993. These rapid actions may modulate nongenomic events, or they may culminate in downstream genomic events.…”