24,25-(OH)2D3 regulates protein kinase C through two distinct phospholipid-dependent mechanisms

Journal of Cellular Physiology
S H HelmZ Schwartz

Abstract

We have previously shown that 24,25-(OH)2D3 plays a major role in resting zone (RC) chondrocyte differentiation and that this vitamin D metabolite regulates protein kinase C (PKC). The aim of the present study was to identify the signal transduction pathway used by 24,25-(OH)2D3 to stimulate PKC activation. Confluent, fourth passage RC cells from rat costochondral cartilage were used to evaluate the mechanism of PKC activation. Treatment of RC cultures with 24,25-(OH)2D3 for 90 min produced a dose-dependent increase in diacylglycerol (DAG). Addition of R59022, a diacylglycerol kinase inhibitor, significantly increased PKC activity in cultures treated with 24,25-(OH)2D3. Addition of dioctanoylglycerol (DOG) to plasma membranes isolated from RC increased PKC activity 447-fold. Addition of pertussis toxin or cholera toxin to control cultures elevated basal PKC activity. When added together with 10(-9) M 24,25-(OH)2D3, there was an additive effect on PKC activity but in cultures treated with 10(-8) M 24,25-(OH)2D3, only the hormone-dependent stimulation of PKC was observed. The phospholipase C inhibitor, U73-122, had no effect on PKC activity, indicating that the DAG produced in response to 24,25-(OH)2D3 is not derived from phospha...Continue Reading

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Citations

May 2, 2002·The Journal of Steroid Biochemistry and Molecular Biology·Z SchwartzB D Boyan
Apr 29, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·V L SylviaB D Boyan
Jun 3, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·H A PedrozoB D Boyan
Jul 3, 2010·The Journal of Steroid Biochemistry and Molecular Biology·J Hurst-KennedyZ Schwartz
Aug 8, 2009·Psychoneuroendocrinology·P TuohimaaA Kalueff
Jul 5, 2002·Critical Reviews in Oral Biology and Medicine : an Official Publication of the American Association of Oral Biologists·B D BoyanZ Schwartz
Oct 12, 2001·Journal of Radiological Protection : Official Journal of the Society for Radiological Protection·L S StarikovichM M Veliky

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