Oxidation of Cholesterol Does Not Alter Significantly Its Uptake into High-Density Lipoprotein Particles

Karilainen, Topi; Timr, Štěpán; Vattulainen, Ilpo; Jungwirth, Pavel

doi:10.1021/acs.jpcb.5b00240

Cited by 6 publications

(9 citation statements)

References 47 publications

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“…The diameter of spherical HDL is approximately 10 nm; therefore, it can be simulated in the same box size as one of the larger discoidal HDLs [44–51]. In contrast, the diameters of LDL and VLDL are approximately 20 and 30 nm, respectively.…”

Section: Review Of Simulation Methodologymentioning

confidence: 99%

“…The convergence of free energy profiles can be accelerated by combining umbrella sampling with Hamiltonian REX, whereby windows are allowed to exchange along the reaction coordinate [86, 87]. This technique was used by Karilainen et al [51] to estimate the free energy of uptake of cholesterol and 7-ketocholesterol into α-HDL.…”

Section: Review Of Simulation Methodologymentioning

confidence: 99%

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Molecular dynamics simulations of lipid nanodiscs

Pourmousa

Pastor

2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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A lipid nanodisc is a discoidal lipid bilayer stabilized by proteins, peptides, or polymers on its edge. Nanodiscs have two important connections to structural biology. The first is associated with high-density lipoprotein (HDL), a particle with a variety of functionalities including lipid transport. Nascent HDL (nHDL) is a nanodisc stabilized by Apolipoprotein A-I (APOA1). Determining the structure of APOA1 and its mimetic peptides in nanodiscs is crucial to understanding pathologies related to HDL maturation and designing effective therapies. Secondly, nanodiscs offer non-detergent membrane-mimicking environments and greatly facilitate structural studies of membrane proteins. Although seemingly similar, natural and synthetic nanodiscs are different in that nHDL is heterogeneous in size, due to APOA1 elasticity, and gradually matures to become spherical. Synthetic nanodiscs, in contrast, should be homogenous, stable, and size-tunable. This report reviews previous molecular dynamics (MD) simulation studies of nanodiscs and illustrates convergence and accuracy issues using results from new multi-microsecond atomistic MD simulations. These new simulations reveal that APOA1 helices take 10-20 μs to rearrange on the nanodisc, while peptides take 2 μs to migrate from the disc surfaces to the edge. These systems can also become kinetically trapped depending on the initial conditions. For example, APOA1 was trapped in a biologically irrelevant conformation for the duration of a 10 μs trajectory; the peptides were similarly trapped for 5 μs. It therefore remains essential to validate MD simulations of these systems with experiments due to convergence and accuracy issues. This article is part of a Special Issue entitled: Emergence of Complex Behavior in Biomembranes edited by Marjorie Longo.

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Section: Review Of Simulation Methodologymentioning

confidence: 99%

Section: Review Of Simulation Methodologymentioning

confidence: 99%

Molecular dynamics simulations of lipid nanodiscs

Pourmousa

Pastor

2018

Biochimica et Biophysica Acta (BBA) - Biomembranes

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“…Reconstructing the free energy profiles for transfer of cholesterol and an oxysterol (7-ketocholesterol) from the water phase into the HDL particle, they showed that both cholesterol and the oxysterol exhibit comparable minima and localize to the surface of the particle. The authors proposed the surface localization of the oxysterols as a potential mechanism for how oxysterols may be involved in signaling …”

Section: How Do Biomembranes Use Lipids To Store Energy?mentioning

confidence: 99%

“…1265 Oxysterols are oxidized cholesterol derivatives. Since oxidation impairs cholesterol uptake from the cells by HDL and is likely to play a signaling role in cholesterol transport, Karilainen et al 1266 investigated the effect of oxidation on spontaneous cholesterol partitioning into the spherical HDL using REUS all-atom simulations. Reconstructing the free energy profiles for transfer of cholesterol and an oxysterol (7ketocholesterol) from the water phase into the HDL particle, they showed that both cholesterol and the oxysterol exhibit comparable minima and localize to the surface of the particle.…”

Section: Chemical Reviewsmentioning

confidence: 99%

Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance

et al. 2019

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Biological membranes are tricky to investigate. They are complex in terms of molecular composition and structure, functional over a wide range of time scales, and characterized by nonequilibrium conditions. Because of all of these features, simulations are a great technique to study biomembrane behavior. A significant part of the functional processes in biological membranes takes place at the molecular level; thus computer simulations are the method of choice to explore how their properties emerge from specific molecular features and how the interplay among the numerous molecules gives rise to function over spatial and time scales larger than the molecular ones. In this review, we focus on this broad theme. We discuss the current state-of-the-art of biomembrane simulations that, until now, have largely focused on a rather narrow picture of the complexity of the membranes. Given this, we also discuss the challenges that we should unravel in the foreseeable future. Numerous features such as the actin-cytoskeleton network, the glycocalyx network, and nonequilibrium transport under ATP-driven conditions have so far received very little attention; however, the potential of simulations to solve them would be exceptionally high. A major milestone for this research would be that one day we could say that computer simulations genuinely research biological membranes, not just lipid bilayers.

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“…Direct elimination of COPs occurs to protect cell functions. Passive diffusion of COPs occurs spontaneously between cells and extracellular lipid‐containing structures such as LDLs and HDLs (Gelissen et al., 1999; Jessup et al., 2002; Karilainen et al., 2015). In serum, it has been proposed that COPs can be transported by LDLs.…”

Section: Biological Fate Of Dietary Copsmentioning

confidence: 99%

Dietary cholesterol oxidation products: Perspectives linking food processing and storage with health implications

Liu

Yang

Xiao

et al. 2021

Comp Rev Food Sci Food Safe

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Dietary cholesterol oxidation products (COPs) are heterogeneous compounds formed during the processing and storage of cholesterol‐rich foods, such as seafood, meat, eggs, and dairy products. With the increased intake of COPs‐rich foods, the concern about health implications of dietary COPs is rising. Dietary COPs may exert deleterious effects on human health to induce several inflammatory diseases including atherosclerosis, neurodegenerative diseases, and inflammatory bowel diseases. Thus, knowledge regarding the effects of processing and storage conditions leading to formation of COPs is needed to reduce the levels of COPs in foods. Efficient methodologies to determine COPs in foods are also essential. More importantly, the biological roles of dietary COPs in human health and effects of phytochemicals on dietary COPs‐induced diseases need to be established. This review summarizes the recent information on dietary COPs including their formation in foods during their processing and storage, analytical methods of determination of COPs, metabolic fate, implications for human health, and beneficial interventions by phytochemicals. The formation of COPs is largely dependent on the heating temperature, storage time, and food matrices. Alteration of food processing and storage conditions is one of the potent strategies to restrict hazardous dietary COPs from forming, including maintaining relatively low temperatures, shorter processing or storage time, and the appropriate addition of antioxidants. Once absorbed into the circulation, dietary COPs can contribute to the progression of several inflammatory diseases, where the absorbed dietary COPs may induce inflammation, apoptosis, and autophagy in cells in the target organs or tissues. Improved intake of phytochemicals may be an effective strategy to reduce the hazardous effects of dietary COPs.

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Oxidation of Cholesterol Does Not Alter Significantly Its Uptake into High-Density Lipoprotein Particles

Cited by 6 publications

References 47 publications

Molecular dynamics simulations of lipid nanodiscs

Molecular dynamics simulations of lipid nanodiscs

Multiscale Simulations of Biological Membranes: The Challenge To Understand Biological Phenomena in a Living Substance

Dietary cholesterol oxidation products: Perspectives linking food processing and storage with health implications

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