1,25(OH)2D3 Regulates Protein Kinase C Activity Through Two Phospholipid-Dependent Pathways Involving Phospholipase A2 and Phospholipase C in Growth Zone Chondrocytes

Sylvia, V. L.; Schwartz, Zvi; Curry, D.; Chang, Zee-Fen; Dean, David D.; Boyan, Barbara D.

doi:10.1359/jbmr.1998.13.4.559

Cited by 59 publications

(36 citation statements)

References 53 publications

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“…In contrast, both cellular PKC and matrix vesicle PKC are regulated by G-protein-dependent mechanisms. As noted for intact cells (38), neither G s nor G i is involved, either in maintenance of PKC activity in control matrix vesicles or in the decrease noted in matrix vesicles treated with 1␣,25(OH) 2 D 3 . However, inhibition of G-protein activity with GDP␤S blocks the effects of 1␣,25(OH) 2 D 3 .…”

Section: ␣25(oh) 2 D 3 Elicits G-protein-dependent Effects On Matrimentioning

confidence: 66%

“…In addition, we examined the direct effect of diacylglycerol (DAG) on matrix vesicle PKC. DAG is the product of PLC action; it is an activator of PKC in growth zone cells and mediates the rapid increase in PKC activity in response to 1␣,25(OH) 2 D 3 (38). Matrix vesicles were incubated with 1, 10, or 100 M DOG for 9 min in the presence and absence of 10 Ϫ8 M 1␣,25(OH) 2 D 3 , and PKC activity was measured.…”

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confidence: 99%

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1α,25(OH)2D3 Regulates Chondrocyte Matrix Vesicle Protein Kinase C (PKC) Directly via G-protein-dependent Mechanisms and Indirectly via Incorporation of PKC during Matrix Vesicle Biogenesis

Schwartz

Sylvia

Larsson

et al. 2002

Journal of Biological Chemistry

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Matrix vesicles are extracellular organelles involved in mineral formation that are regulated by 1␣,25 (OH) 2 D 3 . Prior studies have shown that protein kinase C (PKC) activity is involved in mediating the effects of 1␣,25(OH) 2 D 3 in both matrix vesicles and plasma membranes. Here, we examined the regulation of matrix vesicle PKC by 1␣,25(OH) 2 D 3 during biogenesis and after deposition in the matrix. When growth zone costochondral chondrocytes were treated for 9 min with 1␣,25 (OH) 2 D 3 , PKC in matrix vesicles was inhibited, while PKC␣ in plasma membranes was increased. In contrast, after treatment for 12 or 24 h, PKC in matrix vesicles was increased, while PKC␣ in plasma membranes was unchanged. The effect of 1␣,25(OH) 2 D 3 was stereospecific and metabolite-specific. Monensin blocked the increase in matrix vesicle PKC after 24 h, suggesting the secosteroid-regulated packaging of PKC. In addition, the 1␣,25(OH) 2 D 3 membrane vitamin D receptor (1,25-mVDR) was involved, since a specific antibody blocked the 1␣,25(OH) 2 D 3 -dependent changes in PKC after both long and short treatment times. In contrast, antibodies to annexin II had no effect, and there was no evidence for the presence of the nuclear VDR on Western blots. To investigate the signaling pathways involved in regulating matrix vesicle PKC activity after biosynthesis, matrix vesicles were isolated and then treated for 9 min with 1␣,25(OH) 2 D 3 in the presence and absence of specific inhibitors. Inhibition of phosphatidylinositol-phospholipase C, phospholipase D, or G i /G s had no effect. However, inhibition of G q blocked the effect of 1␣,25(OH) 2 D 3 . The rapid effect of 1␣,25(OH) 2 D 3 also involved the 1,25-mVDR. Moreover, arachidonic acid was found to stimulate PKC when added directly to isolated matrix vesicles. These results indicate that matrix vesicle PKC is regulated by 1␣,25(OH) 2 D 3 at three levels: 1) during matrix vesicle biogenesis; 2) through direct action on the membrane; and 3) through production of other factors such as arachidonic acid.Costochondral growth plate chondrocytes metabolize 25 (OH)D 3 in a regulated manner, producing and secreting 1,25 (OH) 2 D 3 and 24,25(OH) 2 D 3 (1, 2). The physiological importance of this is not yet well understood. 1␣,25(OH) 2 D 3 exerts direct effects on matrix vesicles isolated from the extracellular matrix of growth plate chondrocytes (3), suggesting that the cells may use local production of the vitamin D metabolite as a mechanism for controlling events in the matrix. A number of observations support this hypothesis. Treatment of matrix vesicles with 1␣,25(OH) 2 D 3 causes increased alkaline phosphatase specific activity, which is associated with the onset of calcification (4). In addition, phospholipase A 2 (PLA 2 ) 1 specific activity is increased (5), which may lead to a loss of membrane integrity and the release of proteinases capable of remodeling the matrix (6, 7). One of the matrix metalloproteinases that are present in matrix vesicles, stromelysin-1 (MMP-3), has been shown to ...

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Section: ␣25(oh) 2 D 3 Elicits G-protein-dependent Effects On Matrimentioning

confidence: 66%

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confidence: 99%

1α,25(OH)2D3 Regulates Chondrocyte Matrix Vesicle Protein Kinase C (PKC) Directly via G-protein-dependent Mechanisms and Indirectly via Incorporation of PKC during Matrix Vesicle Biogenesis

Schwartz

Sylvia

Larsson

et al. 2002

Journal of Biological Chemistry

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“…More recently, 1,25(OH) 2 D 3 has also been shown to act as a potent stimulator of cell differentiation, influencing the development of bone and immune cell lineages (Hewison & O'Riordan 1997). The actions of 1,25(OH) 2 D 3 are mediated primarily through interaction with the intracellular vitamin D receptor (VDR) (Haussler et al 1998), although several recent reports have highlighted rapid nongenomic effects of 1,25(OH) 2 D 3 , particularly in cells such as growth-plate chondrocytes (Sylvia et al 1998). Much attention has focused on the role of membrane and nuclear receptors as mediators of both classical and non-classical actions of 1,25(OH) 2 D 3.…”

Section: Introductionmentioning

confidence: 99%

1alpha-Hydroxylase and the action of vitamin D

Hewison¹,

Zehnder²,

Bland³

et al. 2000

Journal of Molecular Endocrinology

199

125

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The active form of vitamin D, 1,25-dihydroxvitamin D 3 (1,25(OH) 2 D 3 ), is a pleiotropic hormone whose actions include the regulation of calcium homeostasis, control of bone cell differentiation and modification of immune responses. Synthesis of 1,25(OH) 2 D 3 from the major circulating metabolite, 25-hydroxyvitamin D 3 (25(OH)D 3 ), is catalysed by a mitochondrial cytochrome P450 enzyme, 25-hydroxyvitamin D-1 -hydroxylase (1 -OHase). Although 1 -OHase is expressed predominantly in the kidney, extra-renal production of 1,25(OH) 2 D 3 has also been demonstrated in tissues such as lymph nodes and skin. The tight regulation of 1 -OHase which occurs in both renal and peripheral tissues has made studies of the expression and regulation of this enzyme remarkably difficult. However, the recent cloning of mouse, rat and human cDNAs for 1 -OHase (CYP1 /Cyp1 ) has enabled a more thorough characterization of this enzyme. In particular, analysis of the CYP1 gene has identified mutations causing the inherited disorder vitamin D-dependent rickets type 1, also known as pseudo-vitamin D deficiency rickets. Studies from our own group have focused on the distribution of 1 -OHase in both renal and extra-renal tissues. Data indicate that the enzyme is expressed throughout the nephron, suggesting discrete endocrine and paracrine/autocrine functions. Further immunohistochemical analyses have shown that the enzyme is widely distributed in extra-renal tissues, and this appears to be due to the same gene product as the kidney. Collectively, these observations have raised important new questions concerning the role of 1 -OHase in vitamin D signalling at a local level. The relationship between expression of protein for 1 -OHase and enzyme activity has yet to be fully characterized and may be dependent on membrane proteins such as megalin. Similarly, elucidation of the mechanisms involved in differential regulation of renal and extra-renal 1,25(OH) 2 D 3 production will be essential to our understanding of the tissue-specific functions of 1 -OHase. These and other issues are discussed in the current review.

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“…(9) 1,25(OH) 2 D 3 also stimulates phospholipase C, increasing inositol trisphosphate and diacylglycerol (DAG) formation. These events result in a rapid increase in protein kinase C (PKC) activity, (10) which is independent of new protein synthesis (11) and can be elicited by hybrid analogs of 1,25(OH) 2 D 3 , which exhibit <0.1% binding affinity for the VDR. (12) Another important, but less studied, metabolite of 25-hydroxyvitamin D 3 (24,25(OH) 2 D 3 ) has been considered a metabolic end product of 25(OH)D 3 without physiological importance.…”

Section: Introductionmentioning

confidence: 99%

“…AA release (8) and prostaglandin production, (9) as well as inositol trisphosphate and DAG production, (10) increased Ca 2+ influx, (7) and increased membrane fluidity. (1) In contrast, 24,25(OH) 2 D 3 decreases PLA 2 (42) and has no effect on phospholipase C. (11) AA release is initially decreased, (8) as is prostaglandin production.…”

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confidence: 99%

Physiological Importance of the 1,25(OH)2D3 Membrane Receptor and Evidence for a Membrane Receptor Specific for 24,25(OH)2D3

Pedrozo

Schwartz

Rimes

et al. 1999

Journal of Bone and Mineral Research

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1,25(OH)2D3 Regulates Protein Kinase C Activity Through Two Phospholipid-Dependent Pathways Involving Phospholipase A2 and Phospholipase C in Growth Zone Chondrocytes

Cited by 59 publications

References 53 publications

1α,25(OH)2D3 Regulates Chondrocyte Matrix Vesicle Protein Kinase C (PKC) Directly via G-protein-dependent Mechanisms and Indirectly via Incorporation of PKC during Matrix Vesicle Biogenesis

1α,25(OH)2D3 Regulates Chondrocyte Matrix Vesicle Protein Kinase C (PKC) Directly via G-protein-dependent Mechanisms and Indirectly via Incorporation of PKC during Matrix Vesicle Biogenesis

1alpha-Hydroxylase and the action of vitamin D

Physiological Importance of the 1,25(OH)2D3 Membrane Receptor and Evidence for a Membrane Receptor Specific for 24,25(OH)2D3

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