Vitamin D-induced ectodomain shedding of TNF receptor 1 as a nongenomic action: D3 vs D2 derivatives
2016
Abstract As a nongenomic action, 1,25-dihydroxyvitamin D 3 (1,25D 3 ) induces L-type Ca 2+ channel-mediated extracellular Ca 2+ influx in human aortic smooth muscle cells (HASMCs), which activates a
disintegrinand metalloprotease 10 (
ADAM10) to cleave and shed the
ectodomainof
tumor necrosis factor receptor 1(TNFR1). In this study, we examined the potencies of other vitamin D 3 and D 2 analogs to stimulate the
ectodomainshedding of TNFR1 in HASMCs. 25-Hydroxyvitamin D 3 (25D 3 ), a precursor of 1,25D 3 , and elocalcitol, an analog of 1,25D 3 , caused
ectodomainshedding of TNFR1 within 30 min, whereas 1,25-dihydroxyvitamin D 2 (1,25D 2 ) and
paricalcitol, a derivative of 1,25D 2 , did not. Both 25D 3 and elocalcitol rapidly induced extracellular Ca 2+ influx and markedly increased intracellular Ca 2+ , while 1,25D 2 and
paricalcitolcaused only small increases in intracellular Ca 2+ . 25D 3 - and elocalcitol-induced TNFR1
ectodomainsheddings were abolished by
verapamiland in Ca 2+ -free media. Both 25D 3 and elocalcitol caused the translocation of
ADAM10to the cell surface, which was inhibited by
verapamil, while 1,25D 2 and
paricalcitoldid not cause
ADAM10translocation. When
ADAM10was depleted by
ADAM10-siRNA, 25D 3 and elocalcitol could not induce
ectodomainshedding of TNFR1. The plasma membrane receptor, endoplasmic reticulum stress protein 57 (ERp57), but not the classic
vitaminD
receptor, mediated the nongenomic action of vitamin D to induce
ectodomainshedding of TNFR1. In summary, like 1,25D 3 , 25D 3 and elocalcitol caused
ADAM10-mediated
ectodomainshedding of TNFR1, whereas 1,25D 2 and
paricalcitoldid not. The difference may depend on their affinities to ERp57 through which extracellular Ca 2+ influx is induced.
Keywords:
-
Correction
-
Source
-
Cite
-
Save
43
References
14
Citations
NaN
KQI