Inhibition of human lymphocyte transformation by oxygenated sterol compounds

Yachnin, Stanley; Hsu, Robert

doi:10.1016/0008-8749(80)90236-1

Cited by 26 publications

(8 citation statements)

References 21 publications

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“…Oxysterols have been shown to be toxic to a variety of cells, including vascular endothelial cells (6-8), smooth muscle cells (2), fibroblasts (9lo), and P-8 15 mastocytoma cells ( 1 1). Cholesterol derivatives such as 25-hydroxycholesterol, an auto-oxidative product of cholesterol, and 26hydroxycholesterol, an enzymatic oxidative product of cholesterol, are potent effectors of cells (6, [12][13]. A suppression of both the viable cell density and cytotoxic changes induced by 25-and 26- bovine pulmonary arterial and human umbilical vein endothelial cells and in bovine and rabbit arterial smooth muscle cells has been observed in our laboratory (14) and elsewhere (1 5).…”

mentioning

confidence: 71%

Cytotoxicity of Oxysterols on Cultured Smooth Muscle Cells from Human Umbilical Arteries

Zhou

Smith

Kummerow

1993

Experimental Biology and Medicine

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The lethal effect of 25- and 26-hydroxycholesterol on smooth muscle cells derived from human umbilical arteries was investigated. The extent of cellular death corresponded with increasing oxysterol concentrations and incubation times. Incubation of the cells with 0.5, 2.5, or 10 micrograms/ml of 25- or 26-hydroxycholesterol revealed a proportionality between the degree of cellular death and oxysterol concentration over the 5 days of the experiment. Correlation coefficients among the degree of cellular death, the exposing period, and oxysterol concentration were significantly different (P < 0.05). However, none of these changes were noted in the smooth muscle cells cultured for 5 days in a medium containing the same concentration of cholesterol or 0.5% ethanol. An increase in the concentration of either serum or cholesterol in the culture medium did not significantly reduce the cytotoxicity of 2.5 micrograms/ml of 26-hydroxycholesterol. The results of this study suggest that oxysterols have an injurious effect on arterial cells, and that the injurious effect could not be altered by cholesterol, which was present at a serum concentration 12 times higher than that of oxysterols.

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confidence: 71%

Cytotoxicity of Oxysterols on Cultured Smooth Muscle Cells from Human Umbilical Arteries

Zhou

Smith

Kummerow

1993

Experimental Biology and Medicine

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“…Oxysterols as a class can exert a variety of biological activities including cytotoxicity ( 13,14 ), regulation of Chol homeostasis (14)(15)(16)(17)(18)(19), suppression of the immune response (20)(21)(22)(23), and interaction with the hedgehog-signaling pathway (24)(25)(26). Most of the known oxysterols are formed from Chol by enzymatic or free radical oxidation (i.e., autoxidation), but other sterols also can be subject to oxidation when elevated levels are present ( 18 ), such as in various Chol biosynthesis disorders, including SLOS ( 9 ).…”

Section: Lipid Extraction Separation and Hplc-apci-ms/ms Analysesmentioning

confidence: 99%

An oxysterol biomarker for 7-dehydrocholesterol oxidation in cell/mouse models for Smith-Lemli-Opitz syndrome

Korade

Rosado

et al. 2011

Journal of Lipid Research

186

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“…In contrast to these studies showing that mevalonic acid is a critical metabolite required for the sustenance of cells programmed to divide or stimulated to divide by other initiators ofcell growth, one of us has reported that addition of mevalonic acid (0.5-10 mM) to cultures of human peripheral blood lymphocytes causes these cells to enter cell cycle from the Go state, to synthesize DNA, and to divide (5,6). Although pure populations of lymphocytes respond poorly to mevalonic acid, their response can be enhanced by a radioresistant cell in a neutrophil-rich (98-99.8%) population isolated from human peripheral blood by the Ficoll/Hypaque technique (7).…”

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confidence: 90%

Neutrophils are required for the DNA synthetic response of human lymphocytes to mevalonic acid: evidence suggesting that a nonsterol product of mevalonate is involved.

Larson¹,

Chung²,

Scanu³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

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Communicated by Leon 0. Jacobson, January 25, 1982 ABSTRACT Human peripheral blood lymphocytes, in the presence of human neutrophils, initiate DNA synthesis and cell cycling when exposed to mevalonic acid. The ability of lymphocytes to respond in this manner is a radiosensitive property of the cells, whereas the help provided by neutrophils is maintained despite their prior exposure to x-irradiation. Other organic acid anions, including precursors of mevalonic acid biosynthesis and a variety ofproducts ofmevalonate metabolism, fail to initiate DNA synthesis when added to human lymphocytes. Because only the metabolically active R(-) enantiomer of mevalonic acid initiates lymphocyte DNA synthesis, we presume that physiological pathways of mevalonate metabolism are involved. The response to mevalonic acid of ML-236B (compactin)-inhibited lymphocytes is increased, and the threshold concentration ofmevalonate at which lymphocyte DNA synthesis first appears is decreased, when the cells are cultured in lipoprotein-containing (as opposed to lipoprotein-depleted) medium. The response to mevalonic acid oflymphocytes cultured in lipoprotein-depleted medium can be enhanced by addition to the cultures of low density lipoprotein but not by addition of high density lipoprotein. Based upon the flux diversion hypothesis of mevalonate metabolism, these observations suggest that a nonsterol product of mevalonate metabolism may be responsible for the initiation oflymphocyte DNA synthesis by mevalonic acid.

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Inhibition of human lymphocyte transformation by oxygenated sterol compounds

Cited by 26 publications

References 21 publications

Cytotoxicity of Oxysterols on Cultured Smooth Muscle Cells from Human Umbilical Arteries

Cytotoxicity of Oxysterols on Cultured Smooth Muscle Cells from Human Umbilical Arteries

An oxysterol biomarker for 7-dehydrocholesterol oxidation in cell/mouse models for Smith-Lemli-Opitz syndrome

Neutrophils are required for the DNA synthetic response of human lymphocytes to mevalonic acid: evidence suggesting that a nonsterol product of mevalonate is involved.

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