Effects of cholesterol on thermal stability of discoidal high density lipoproteins

Jayaraman, Sundararajan; Benjwal, Sangeeta; Gantz, Donald; Gursky, Olga

doi:10.1194/jlr.m000117

Cited by 15 publications

(26 citation statements)

References 55 publications

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“…The thermodynamic irreversibility of the heat denaturation of various rHDL, which was reported previously, 17,29,36 is evident from the hysteresis in the CD melting data (Figure 4B) and from the observation of lower apparent melting temperatures ( T m,app ) at slower heating rates. 36 As a result, increasing the heating rate from 11 °C/h (in CD experiments) to 90 °C/h (in DSC experiments) led to an increase in the T m,app of apoA-I:DPPC:Ch complexes from 88 to 103 °C (Figure 4B,C).…”

Section: Resultssupporting

confidence: 77%

“…DSC data of lipid-free apoA-I showed a broad peak centered at 60 °C ( T m ) corresponding to protein unfolding, while apoA-I:DMPC rHDL showed two characteristic heat capacity peaks. The peak at T c = 26 °C reflects the chain melting transition in DMPC-containing rHDL, and the peak at 88 °C ( T m,app ) reflects heat denaturation of rHDL (ref 29 and references therein). DSC data in Figure 5A show that, in agreement with the earlier study of a similar system, 37 increasing the lipid:protein ratio led to a gradual conversion of lipid-free apoA-I into rHDL.…”

Section: Resultsmentioning

confidence: 99%

“…This contrasts with the hysteresis and large scan rate effects observed in the melting data of rHDL and HDL, which are hallmarks of irreversible kinetically controlled transitions (Figure 4B). 14,18,29,36 Hence, in contrast to irreversible unfolding of apoA-I in lipoproteins, the unfolding of free apoA-I in solution or in the presence of POPC SUV is thermodynamically reversible. Taken together, our results are consistent with the adsorption of apoA-I to the vesicle surface, as opposed to penetration of the protein into the lipid surface which involves high kinetic barriers.…”

Section: Resultsmentioning

confidence: 99%

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Pressure Perturbation Calorimetry of Lipoproteins Reveals an Endothermic Transition without Detectable Volume Changes. Implications for Adsorption of Apolipoprotein to a Phospholipid Surface

et al. 2011

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Plasma lipoproteins are assemblies of lipids and apolipoproteins that mediate lipid transport and metabolism. High-density lipoproteins (HDL) remove excess cell cholesterol and provide protection against atherosclerosis. Important aspects of metabolic HDL remodeling, including apolipoprotein dissociation and lipoprotein fusion, are mimicked in thermal denaturation. We report the first study of the protein–lipid complexes by pressure perturbation calorimetry (PPC) beyond 100 °C. In PPC, volume expansion coefficient αv(T) is measured during heating; in proteins, αv(T) is dominated by hydration. Calorimetric studies of reconstituted HDL and of human high-density, low-density, and very low-density lipoproteins reveal that apolipoprotein unfolding, dissociation, and lipoprotein fusion are endothermic transitions without detectable volume changes. This may result from the limited applicability of PPC to slow kinetically controlled transitions such as thermal remodeling of lipoproteins and/or from the possibility that this remodeling causes no significant changes in the solvent structure and, hence, may not involve large transient solvent exposure of apolar moieties. Another conclusion is that apolipoprotein A-I in solution adsorbs to the phospholipid surface; protein hydration is preserved upon such adsorption. We posit that adsorption to a phospholipid surface helps recruit free apolipoprotein to the plasma membrane and facilitate HDL biogenesis.

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Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Pressure Perturbation Calorimetry of Lipoproteins Reveals an Endothermic Transition without Detectable Volume Changes. Implications for Adsorption of Apolipoprotein to a Phospholipid Surface

et al. 2011

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“…However, cholesterol by itself does not form lipid-protein complex particles with apolipoprotein, though it may directly bind to some proteins such as serum albumin (Ha et al, 2003;Peng et al, 2008). To the contrary, physicochemical assembly of the HDL-like particles, similarly to those produced by the ABCA1-mediated cell-apolipoprotein interaction may not essentially require cholesterol (Fukuda et al, 2010;Jayaraman et al, 2010). Also, HDL-like particles can be generated even without cholesterol upon the ABCA1-mediated cell-apolipoprotein interaction (Yamauchi et al, 2002).…”

Section: Discussionmentioning

confidence: 92%

Preferential incorporation of shorter and less unsaturated acyl phospholipids into high density lipoprotein-like particles in the ABCA1- and ABCA7-mediated biogenesis with apoA-I

Hotta

Abe-Dohmae

Taguchi

et al. 2015

Chemistry and Physics of Lipids

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“…16 However, in the reverse cholesterol pathway, an increase in the nonamphipathic cholesterol content in HDL leads to the conversion of the discoidal structure to a spherical structure and destabilization of apolipoprotein A-I binding, which results in structural disorder at the HDL surface. 17 Thus, we hypothesized that exclusion of phospholipids during the assembly of HDL-like nanoparticles may result in sensitivity to environmental changes, such as a pH decrease, because of the expected disordered structure of the HDL in the absence of phospholipids.…”

Section: Introductionmentioning

confidence: 99%

pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy

Shin

Yang²,

Heo³

et al. 2012

IJN

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Background: Nanoparticles undergoing physicochemical changes to release enclosed drugs at acidic pH conditions are promising vehicles for antitumor drug delivery. Among the various drug carriers, high-density lipoprotein (HDL)-like nanoparticles have been shown to be beneficial for cancer chemotherapy, but have not yet been designed to be pH-responsive. Methods and results:In this study, we developed a pH-responsive HDL-like nanoparticle that selectively releases paclitaxel, a model antitumor drug, at acidic pH. While the well known HDL-like nanoparticle containing phospholipids, phosphatidylcholine, and apolipoprotein A-I, as well as paclitaxel (PTX-PL-NP) was structurally robust at a wide range of pH values (3.8-10.0), the paclitaxel nanoparticle that only contained paclitaxel and apoA-I selectively released paclitaxel into the medium at low pH. The paclitaxel nanoparticle was stable at physiological and basic pH values, and over a wide range of temperatures, which is a required feature for efficient cancer chemotherapy. The homogeneous assembly enabled high paclitaxel loading per nanoparticle, which was 62.2% (w/w). The molar ratio of apolipoprotein A-I and paclitaxel was 1:55, suggesting that a single nanoparticle contained approximately 110 paclitaxel particles in a spherical structure with a 9.2 nm diameter. Among the several reconstitution methods applied, simple dilution following sonication enhanced the reconstitution yield of soluble paclitaxel nanoparticles, which was 0.66. As a result of the pH responsiveness, the anticancer effect of paclitaxel nanoparticles was much more potent than free paclitaxel or PTX-PL-NP. Conclusion: The anticancer efficacy of both paclitaxel nanoparticles and PTX-PL-NP was dependent on the expression of scavenger receptor class B type I, while the killing efficacy of free paclitaxel was independent of this receptor. We speculate that the pH responsiveness of paclitaxel nanoparticles enabled efficient endosomal escape of paclitaxel before lysosomal break down. This is the first report on pH-responsive nanoparticles that do not contain any synthetic polymer.

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Effects of cholesterol on thermal stability of discoidal high density lipoproteins

Cited by 15 publications

References 55 publications

Pressure Perturbation Calorimetry of Lipoproteins Reveals an Endothermic Transition without Detectable Volume Changes. Implications for Adsorption of Apolipoprotein to a Phospholipid Surface

Pressure Perturbation Calorimetry of Lipoproteins Reveals an Endothermic Transition without Detectable Volume Changes. Implications for Adsorption of Apolipoprotein to a Phospholipid Surface

Preferential incorporation of shorter and less unsaturated acyl phospholipids into high density lipoprotein-like particles in the ABCA1- and ABCA7-mediated biogenesis with apoA-I

pH-responsive high-density lipoprotein-like nanoparticles to release paclitaxel at acidic pH in cancer chemotherapy

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