Mechanisms of resistance to the cytotoxic effects of oxysterols in human leukemic cells

Gregorio-King, Claudia C.; Gough, Tamara J.; Meer, Gavin J Van Der; Hosking, Jane B; Waugh, Caryll; McLeod, Janet; Collier, Fiona; Kirkland, Mark

doi:10.1016/j.jsbmb.2003.12.007

Cited by 18 publications

(19 citation statements)

References 32 publications

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“…This ability of 7KC to induce different modes of cell death depending on the cell type considered was also reported on the cells of the vascular wall [17]. 7b-OHC, known as an inducer of a calcium-independent apoptosis in U937 cells and HL-60 [19,55] induced an accumulation of intracellular Ca 2+ in SK-N-BE cells but not caspase 3 cleavage nor DNA fragmentation. Ryan et al [19] reported that treating U937 cells with Ca 2+ channel blockers did not protect them from apoptosis induced by 7b-OHC.…”

Section: Discussionsupporting

confidence: 68%

Effects of cholesterol oxides on cell death induction and calcium increase in human neuronal cells (SK-N-BE) and evaluation of the protective effects of docosahexaenoic acid (DHA; C22:6 n-3)

et al. 2015

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Section: Discussionsupporting

confidence: 68%

Effects of cholesterol oxides on cell death induction and calcium increase in human neuronal cells (SK-N-BE) and evaluation of the protective effects of docosahexaenoic acid (DHA; C22:6 n-3)

et al. 2015

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“…Remarkably, the same treatments to frozen/thawed sperm did not result in the formation of oxysterols or in the albuminmediated depletion of cholesterol (and oxidized products). Many studies have been performed that suggest that cytotoxicity of oxysterols may result from the induction of apoptosis [15,[49][50][51][52][53][54][55][56][57]. Sperm cells themselves appear to be well protected for apoptosis because of the absence of cytosol (containing the apoptotic machinery) and the hypercondensation of DNA (preventing fragmentation [58]), but sperm cells loaded with oxysterols could turn out to be poor matches for the egg cell they fertilize.…”

Section: Oxysterol Formation In and Depletion From Sperm Cellsmentioning

confidence: 99%

Mass Spectrometric Detection of Cholesterol Oxidation in Bovine Sperm1

Brouwers

Boerke

Silva

et al. 2011

Biology of Reproduction

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We report on the presence and formation of cholesterol oxidation products (oxysterols) in bovine sperm. Although cholesterol is the most abundant molecule in the membrane of mammalian cells and is easily oxidized, this is the first report on cholesterol oxidation in sperm membranes as investigated by state-of-the-art liquid chromatographic and mass spectrometric methods. First, oxysterols are already present in fresh semen samples, showing that lipid peroxidation is part of normal sperm physiology. After chromatographic separation (by high-performance liquid chromatography), the detected oxysterol species were identified with atmospheric pressure chemical ionization mass spectrometry in multiple-reaction-monitoring mode that enabled detection in a broad and linear concentration range (0.05-100 pmol for each oxysterol species detected). Second, exposure of living sperm cells to oxidative stress does not result in the same level and composition of oxysterol species compared with oxidative stress imposed on reconstituted vesicles from protein-free sperm lipid extracts. This suggests that living sperm cells protect themselves against elevated oxysterol formation. Third, sperm capacitation induces the formation of oxysterols, and these formed oxysterols are almost completely depleted from the sperm surface by albumin. Fourth, and most importantly, capacitation after freezing/thawing of sperm fails to induce both the formation of oxysterols and the subsequent albumin-dependent depletion of oxysterols from the sperm surface. The possible physiological relevance of capacitation-dependent oxysterol formation and depletion at the sperm surface as well as the omission of this after freezing/thawing semen is discussed.

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“…In addition, other studies have implicated changes in intracellular Ca 2+ as part of the signaling process in oxysterol-induced apoptosis [15][16][17][18][19]. A study by Gregorio-King et al [20] investigated the effects of three individual oxysterols on HL-60 cells. The Ca 2+ channel blocker nifedipine prevented apoptosis induced by 25-hydroxycholesterol (25-OH) but did not protect against 7β-hydroxycholesterol (7β-OH)-or 7-ketoinduced cell death.…”

Section: Introductionmentioning

confidence: 99%

The role of calcium in apoptosis induced by 7β‐hydroxycholesterol and cholesterol‐5β,6β‐epoxide

Lordan

O’Brien

Mackrill

2009

J Biochem & Molecular Tox

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Oxysterols, such as 7beta-hydroxy-cholesterol (7beta-OH) and cholesterol-5beta,6beta-epoxide (beta-epoxide), may have a central role in promoting atherogenesis. This is thought to be predominantly due to their ability to induce apoptosis in cells of the vascular wall and in monocytes/macrophages. Although there has been extensive research regarding the mechanisms through which oxysterols induce apoptosis, much remains to be clarified. Given that experimental evidence has long associated alterations of calcium (Ca(2+)) homeostasis to apoptotic cell death, the aim of the present study was to determine the influence of intracellular Ca(2+) changes on apoptosis induced by 7beta-OH and beta-epoxide. Ca(2+) responses in differentiated U937 cells were assessed by epifluorescence video microscopy, using the ratiometric dye fura-2. Over 15-min exposure of differentiated U937 cells to 30 muM of 7beta-OH induced a slow but significant rise in fura-2 ratio. The Ca(2+) channel blocker nifedipine and the chelating agent EGTA blocked the increase in cytoplasmic Ca(2+). Moreover, dihydropyridine (DHP) binding sites identified with BODIPY-FLX-DHP were blocked following pretreatment with nifedipine, indicating that the influx of Ca(2+) occurred through L-type channels. However, following long-term incubation with 7beta-OH, elevated levels of cytoplasmic Ca(2+) were not maintained and nifedipine did not provide protection against apoptotic cell death. Our results indicate that the increase in Ca(2+) may be an initial trigger of 7beta-OH-induced apoptosis, but following chronic exposure to the oxysterol, the influence of Ca(2+) on apoptotic cell death appears to be less significant. In contrast, Ca(2+) did not appear to be involved in beta-epoxide-induced apoptosis.

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Mechanisms of resistance to the cytotoxic effects of oxysterols in human leukemic cells

Cited by 18 publications

References 32 publications

Effects of cholesterol oxides on cell death induction and calcium increase in human neuronal cells (SK-N-BE) and evaluation of the protective effects of docosahexaenoic acid (DHA; C22:6 n-3)

Effects of cholesterol oxides on cell death induction and calcium increase in human neuronal cells (SK-N-BE) and evaluation of the protective effects of docosahexaenoic acid (DHA; C22:6 n-3)

Mass Spectrometric Detection of Cholesterol Oxidation in Bovine Sperm1

The role of calcium in apoptosis induced by 7β‐hydroxycholesterol and cholesterol‐5β,6β‐epoxide

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