WEDNESDAY, Oct. 8 (HealthDay News) -- The receptor that mediates the actions of vitamin D can be cleaved by a protease activated during cell death and other cellular processes, possibly limiting its activity, according to study findings published online Oct. 1 in Endocrinology.
Peter J. Malloy, Ph.D., and David Feldman, M.D., from Stanford University School of Medicine in Stanford, Calif., examined whether the vitamin D receptor (VDR) was affected by apoptosis (programmed cell death) and activation of caspases (proteases activated during apoptosis and other cellular processes) in vitro.
The researchers found that induction of apoptosis and activation of caspase-3 and caspase-7 blocked the binding of the active form of vitamin D and reduced the levels of VDR. Mutation of two amino acids in the VDR led to its inability to be cleaved by caspase-3, and the wild-type VDR could also be cleaved in vitro by caspase-6 and caspase-7. Treating cells with a proteosome inhibitor blocked further degradation of VDR after caspase cleavage, the investigators report.
"In conclusion, our results demonstrate that the human VDR is a target of caspase-3 and suggest that activation of caspase-3 may limit VDR activity," the authors write.
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