Mechanism of the activation of arachidonic acid release by oxysterols in NRK 49F cells: Role of calcium

Lahoua, Z.; Astruc, M.; Barjon, Jean-Noël; Michel, Françoise; Paulet, A. Crastes de

doi:10.1016/0898-6568(89)90065-x

Cited by 8 publications

(4 citation statements)

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“…( 44 ) Activation of PLA 2 releases arachidonic acid from cellular phospholipids and makes it available for further metabolism by COX enzymes into prostaglandins. ( 54,55 ) Consistent with previous reports of oxysterol‐stimulated metabolism of arachidonic acid, ( 56,57 ) the present results suggest that the osteogenic activity of the oxysterols in MSC are in part mediated by the activation of PLA 2 ‐induced arachidonic acid release and its metabolism into osteogenic prostanoids by the COX pathway. Furthermore, COX activity also seems to be important in regulating the synergism between the osteogenic oxysterols and BMP2, but not in the anti‐adipogenic effects of the oxysterols, suggesting the specific role of COX/PLA 2 pathway in mediating the oxysterol‐induced lineage specific differentiation of M2 cells into osteogenic cells.…”

Section: Discussionsupporting

confidence: 92%

Oxysterols Regulate Differentiation of Mesenchymal Stem Cells: Pro-Bone and Anti-Fat

Kha

Basseri

Shouhed

et al. 2004

Journal of Bone and Mineral Research

163

210

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Pluripotent mesenchymal stem cells can undergo lineage-specific differentiation in adult organisms. However, understanding of the factors and mechanisms that drive this differentiation is limited. We show the novel ability of specific oxysterols to regulate lineage-specific differentiation of mesenchymal stem cells into osteogenic cells while inhibiting their adipogenic differentiation. Such effects may have important implications for intervention with osteoporosis.Introduction: Oxysterols are products of cholesterol oxidation and are formed in vivo by a variety of cells including osteoblasts. Novel pro-osteogenic and anti-adipogenic effects of specific oxysterols on pluripotent mesenchymal cells are demonstrated in this report. Aging and osteoporosis are associated with a decrease in the number and activity of osteoblastic cells and a parallel increase in the number of adipocytic cells. Materials and Methods:The M2-10B4 pluripotent marrow stromal cell line, as well as several other mesenchymal cell lines and primary marrow stromal cells, was used to assess the effects of oxysterols. All results were analyzed for statistical significance using ANOVA. Results and Conclusion: Pro-osteogenic and anti-adipogenic effects of specific oxysterols were assessed by the increase in early and late markers of osteogenic differentiation, including alkaline phosphatase activity, osteocalcin mRNA expression and mineralization, and the decrease in markers of adipogenic differentiation including lipoprotein lipase and adipocyte P2 mRNA expression and adipocyte formation. Complete osteogenic differentiation of M2 cells into cells expressing early and late markers of differentiation was achieved only when using combinations of specific oxysterols, whereas inhibition of adipogenesis could be achieved with individual oxysterols. Oxysterol effects were in part mediated by extracellular signal-regulated kinase and enzymes in the arachidonic acid metabolic pathway, i.e., cyclo-oxygenase and phospholipase A 2 . Furthermore, we show that these specific oxysterols act in synergy with bone morphogenetic protein 2 in inducing osteogenic differentiation. These findings suggest that oxysterols may play an important role in the differentiation of mesenchymal stem cells and may have significant, previously unrecognized, importance in stem cell biology and potential therapeutic interventions.

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Section: Discussionsupporting

confidence: 92%

Oxysterols Regulate Differentiation of Mesenchymal Stem Cells: Pro-Bone and Anti-Fat

Kha

Basseri

Shouhed

et al. 2004

Journal of Bone and Mineral Research

163

210

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“…Most of the effect of 25-OH-Chol on arachidonate release appeared to be due to an effect on arachidonate release from phosphatidylinositol. The stimulating effect of oxysterols on arachidonate release and on prostaglandin formation occurred in the absence of Ca 2ϩ in the external medium or when cellular Ca 2ϩ stores were depleted (533). The oxysterols (25-OH-Chol, 7␣-OH-Chol, and 7␤-OH-Chol, at a concentration of 12.4 M) showed no Ca 2ϩ ionophoretic properties by themselves.…”

Section: U Oxysterols and Signal Transductionmentioning

confidence: 98%

“…The oxysterols (25-OH-Chol, 7␣-OH-Chol, and 7␤-OH-Chol, at a concentration of 12.4 M) showed no Ca 2ϩ ionophoretic properties by themselves. However, the oxysterols potentiated the arachidonate release induced by ionomycin (a Ca 2ϩ ionophore) (533). It was concluded that the oxysterol effects on arachidonate release and on prostaglandin biosynthesis are probably mediated by a mechanism other than one involving a direct effect on Ca 2ϩ metabolism (533).…”

Section: U Oxysterols and Signal Transductionmentioning

confidence: 99%

“…However, the oxysterols potentiated the arachidonate release induced by ionomycin (a Ca 2ϩ ionophore) (533). It was concluded that the oxysterol effects on arachidonate release and on prostaglandin biosynthesis are probably mediated by a mechanism other than one involving a direct effect on Ca 2ϩ metabolism (533). The results of this study and a subsequent investigation (535) suggested that the effects of oxysterols on arachidonate release are synergistic, but not fully dependent on direct effects of the oxysterols on protein kinase C or on Ca 2ϩ metabolism.…”

Section: U Oxysterols and Signal Transductionmentioning

confidence: 99%

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Oxysterols: Modulators of Cholesterol Metabolism and Other Processes

Schroepfer

2000

Physiological Reviews

877

687

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Oxygenated derivatives of cholesterol (oxysterols) present a remarkably diverse profile of biological activities, including effects on sphingolipid metabolism, platelet aggregation, apoptosis, and protein prenylation. The most notable oxysterol activities center around the regulation of cholesterol homeostasis, which appears to be controlled in part by a complex series of interactions of oxysterol ligands with various receptors, such as the oxysterol binding protein, the cellular nucleic acid binding protein, the sterol regulatory element binding protein, the LXR nuclear orphan receptors, and the low-density lipoprotein receptor. Identification of the endogenous oxysterol ligands and elucidation of their enzymatic origins are topics of active investigation. Except for 24, 25-epoxysterols, most oxysterols arise from cholesterol by autoxidation or by specific microsomal or mitochondrial oxidations, usually involving cytochrome P-450 species. Oxysterols are variously metabolized to esters, bile acids, steroid hormones, cholesterol, or other sterols through pathways that may differ according to the type of cell and mode of experimentation (in vitro, in vivo, cell culture). Reliable measurements of oxysterol levels and activities are hampered by low physiological concentrations (approximately 0.01-0.1 microM plasma) relative to cholesterol (approximately 5,000 microM) and by the susceptibility of cholesterol to autoxidation, which produces artifactual oxysterols that may also have potent activities. Reports describing the occurrence and levels of oxysterols in plasma, low-density lipoproteins, various tissues, and food products include many unrealistic data resulting from inattention to autoxidation and to limitations of the analytical methodology. Because of the widespread lack of appreciation for the technical difficulties involved in oxysterol research, a rigorous evaluation of the chromatographic and spectroscopic methods used in the isolation, characterization, and quantitation of oxysterols has been included. This review comprises a detailed and critical assessment of current knowledge regarding the formation, occurrence, metabolism, regulatory properties, and other activities of oxysterols in mammalian systems.

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Oxysterol activation of arachidonic acid release and protaglindin E2 biosynthesis in NRK 49F cells is partially dependent on protein kinase activity

Lahoua

Vial

Michel³

et al. 1991

Cellular Signalling

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Mechanism of the activation of arachidonic acid release by oxysterols in NRK 49F cells: Role of calcium

Cited by 8 publications

References 18 publications

Oxysterols Regulate Differentiation of Mesenchymal Stem Cells: Pro-Bone and Anti-Fat

Oxysterols Regulate Differentiation of Mesenchymal Stem Cells: Pro-Bone and Anti-Fat

Oxysterols: Modulators of Cholesterol Metabolism and Other Processes

Oxysterol activation of arachidonic acid release and protaglindin E2 biosynthesis in NRK 49F cells is partially dependent on protein kinase activity

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