IndraLab

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Cholesterol inhibits KCNMA1. 35 / 37
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"SLO was inhibited by cholesterol, cortisol, and specific antibody in vitro ; pretreatment of animals with cortisone decreased the susceptibility of their isolated lysosomes to SLO."
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"Depletion of cholesterol from erythrocyte membranes was shown to impair binding of PFO, but not ILY or SLO, due to the presence of its CD59 receptor for the former and likely due to its galactose containing carbohydrate receptor for the latter."
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"Cholesterol inhibition of slo1 channels is Ca2+-dependent and can be mediated by either high-affinity Ca2+-sensing site in the slo1 cytosolic tail."
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"The KCa1.1 protein was reduced by cholesterol enrichment with MbetaCD-cholesterol, and the effect was reversed by the lysosomal inhibition with bafilomycin A1 or the proteasome inhibition with lactacystin."
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"Our data demonstrate that BK channel inhibition by cholesterol and related analogues strictly depends on the β configuration of the sterol C3 hydroxyl and is facilitated by the hydrophobic nature of the side chain, while having rather lax structural requirements on the A/B ring fusion within the hydrophobic steroid ring system."
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"Interestingly, cholesterol completely inhibits the cytotoxicity of 0.8 mug/ml PLY and 1.5 mug/ml SLO, and also abrogates their platelet aggregation inducing abilities."
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"We conclude that dietary cholesterol protects against AICAC by cholesterol buildup in the arterial tissue and diminished function (but not surface presence) of EtOH target - BK channel."
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"Moreover we have recently identified distinct amino acids that form several cholesterol sensing sites on BK channel forming (alpha) subunit and are responsible for cholesterol induced BK channel inhibition."
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"Therefore, BK channel inhibition by CLR selectively requires optimal levels of Ca 2+ being recognized by either of the slo1 high-affinity Ca 2+ -sensing sites."
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"From these early studies, it became accepted that cholesterol reduction of BK channel activity is determined by changes in physical properties of the bulk membrane lipid that occur upon sterol insertion into the bilayer."
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"SLO was inhibited by cholesterol, cortisol, and specific antibody in vitro; pretreatment of animals with cortisone decreased the susceptibility of their isolated lysosomes to SLO."
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"Because SLO is a member of the cholesterol dependent cytolysin family, we hypothesized that ABCA1 causes a change in the cholesterol content of the PM, thereby reducing binding of SLO to the PM."
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"The SLO syndrome is caused by a block in the cholesterol biosynthesis due to the autosomal recessive deficiency of 7-dehydrocholesterol reductase."
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"Therefore, steroid molecular area per se or its possible contribution to bilayer stress is unlikely to underlie the differential degree of BK channel inhibition caused by cholesterol and related monohydroxysterols."
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"Moreover we have recently identified distinct amino acids that form several cholesterol-sensing sites on BK channel-forming (α) subunit and are responsible for cholesterol-induced BK channel inhibition ( xref )."
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"Dietary cholesterol did not down-regulate membrane surface presence of ethanol target - vascular smooth muscle BK channel (XREF_FIG), but ablated BK channel function (XREF_FIG)."
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"Thus, there seems to be an optimal level of cholesterol to fully enable ethanol inhibition of BK channel function and reduction of cerebral artery diameter."
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"Two major findings from our study point to the involvement of a specific sterol recognition protein site (s) in cholesterol inhibition of BK channel activity : first, the beta configuration of the C3 hydroxyl is necessary for channel inhibition, as cholesterol is effective and its C3 alpha epimer (epicholesterol) is not."
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"Supernatant was aliquoted into two tubes; 25 µg of water-soluble cholesterol (inhibitor for SLO activity) was added to one."
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"In contrast, cholesterol inhibits BK channel activity."
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"Significance Statement Results reveal that the widely reported inhibition of BK (slo1) channels by membrane cholesterol requires a physiologically range of internal Ca 2+ and is selectively linked to the two high-affinity Ca 2+ -sensing sites located in the cytosolic tail domain of slo1 proteins, which underscores that Ca 2+ and cholesterol actions are allosterically coupled to the channel gate."
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"Increased cholesterol in the plasma membrane can diminish the alcohol potentiation of the BK channel, potentially contributing to channel tolerance."
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"Our data demonstrate that BK channel inhibition by cholesterol and related analogues strictly depends on the beta configuration of the sterol C3 hydroxyl and is facilitated by the hydrophobic nature of the side chain, while having rather lax structural requirements on the A/B ring fusion within the hydrophobic steroid ring system."
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"A simpler and more plausible explanation is that cbv1 itself contains the site (s) for cholesterol sensing and binding that is responsible for cholesterol reduction of BK channel activity."
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"Thus, our data buttress the idea that BK channel forming alpha subunits and a bare lipid environment (e.g., a binary phospholipid bilayer) are sufficient to support cholesterol induced reduction of BK channel activity."
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"It has been reported that cholesterol enrichment suppresses BK channel activity in human melanoma IGR39 cells XREF_BIBR and in reconstituted channels in lipid bilayers XREF_BIBR."
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"Increased cholesterol in the bilayer (which will increase membrane thickness and rigidity and promote formation of lipid rafts) can diminish the alcohol potentiation of the BK channel [XREF_BIBR], potentially contributing to channel tolerance."
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"This artificial addition of cholesterol led to the predicted increase in infected erythrocyte SLO lysis, closely mimicking the reduced SLO lytic discrimination observed upon immediate acquisition of clinical samples from patients (47.5% lysis and 47.8% lysis in clinical ex vivo and cholesterol supplemented in vitro samples, respectively, when treated with ~30U SLO; Fig. 6, black circles)."
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"Furthermore, it has been consistently interpreted that cholesterol reduction of BK channel activity is primarily determined by changes in the physical properties of the bulk lipid bilayer upon cholesterol insertion in the bilayer."
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"However, cholesterol enrichment did not induce BK channel suppression in hKCa1.1-HEK 293 cells that do not express the beta1-subunit."
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"Cholesterol inhibition of slo1 channels is Ca2+-dependent and can be mediated by either high-affinity Ca2+-sensing site in the slo1 cytosolic tail."
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"Streptococcal strains expressing significant SLO activity at their saturating amounts required 40min to carry out complete hemolysis, whereas, after inhibition of SLO by cholesterol containing liposomes, the remaining SLS activity developed much slower, requiring 80-160min to reach its full extent."
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"KCa1.1 protein was also decreased by cholesterol enrichment with MbetaCD-cholesterol or LDL in human coronary artery smooth muscle cells."
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"Data demonstrated that cholesterol at a bilayer molar fraction within the range found in natural membranes reduced the steady-state activity (Po) of recombinant BK channel forming cbv1 protein obtained from rat cerebral artery myocytes."
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"The alpha subunit contains several conserved cholesterol recognition amino acid consensus (CRAC) motifs that may constitute the binding sites by which cholesterol inhibits BK channel activity in the absence of beta subunits, while the beta subunits also contain two CRAC motifs (32)."
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