Effects of Membrane Cholesterol on Stability of Transmembrane Helix Associations

Yano, Yoshiaki

doi:10.1248/cpb.c22-00144

Cited by 3 publications

(1 citation statement)

References 43 publications

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“…42,43) The cholesterol homeostasis disorder is considered one of the manifestations of cancer. 44) In the field of prostate cancer research, it is crucial to find drugs and treatment options targeting cholesterol.…”

Section: Discussionmentioning

confidence: 99%

Anticancer Activity of Methyl Protodioscin against Prostate Cancer by Modulation of Cholesterol-Associated MAPK Signaling Pathway <i>via</i> FOXO1 Induction

Chen

Qin

Tao

et al. 2023

Biological & Pharmaceutical Bulletin

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Methyl protodioscin (MPD), a furostanol saponin found in the rhizomes of Dioscoreaceae, has lipidlowering and broad anticancer properties. However, the efficacy of MPD in treating prostate cancer remains unexplored. Therefore, the present study aimed to evaluate the anticancer activity and action mechanism of MPD in prostate cancer. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), wound healing, transwell, and flow cytometer assays revealed that MPD suppressed proliferation, migration, cell cycle, and invasion and induced apoptosis of DU145 cells. Mechanistically, MPD decreased cholesterol concentration in the cholesterol oxidase, peroxidase and 4-aminoantipyrine phenol (COD-PAP) assay, disrupting the lipid rafts as detected using immunofluorescence and immunoblot analyses after sucrose density gradient centrifugation. Further, it reduced the associated mitogen-activated protein kinase (MAPK) signaling pathway protein P-extracellular regulated protein kinase (ERK), detected using immunoblot analysis. Forkhead box O (FOXO)1, a tumor suppressor and critical factor controlling cholesterol metabolism, was predicted to be a direct target of MPD and induced by MPD. Notably, in vivo studies demonstrated that MPD significantly reduced tumor size, suppressed cholesterol concentration and the MAPK signaling pathway, and induced FOXO1 expression and apoptosis in tumor tissue in a subcutaneous mouse model. These results suggest that MPD displays anti-prostate cancer activity by inducing FOXO1 protein, reducing cholesterol concentration, and disrupting lipid rafts. Consequently, the reduced MAPK signaling pathway suppresses proliferation, migration, invasion, and cell cycle and induces apoptosis of prostate cancer cells.

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Section: Discussionmentioning

confidence: 99%

Anticancer Activity of Methyl Protodioscin against Prostate Cancer by Modulation of Cholesterol-Associated MAPK Signaling Pathway <i>via</i> FOXO1 Induction

Chen

Qin

Tao

et al. 2023

Biological & Pharmaceutical Bulletin

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Effects of Gly Residue and Cholesterol on the GXXXG‐Mediated Parallel Association of Transmembrane Helices: A Single‐Pair FRET Study

Yano

Morise

2022

ChemBioChem

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Small residue-mediated interhelical packing is ubiquitous in helical membrane proteins: however, the lipid dependence of its stability remains unclear. We previously demonstrated that the introduction of a GXXXG sequence in the middle of de novo-designed (AALALAA) 3 helices (AALALAA AGLALGA AALA-LAA) facilitated their dimerization, which was abolished by cholesterol. Here single-pair FRET measurements revealed that a longer GXXXGXXXG segment (AALALAA A GLALGA AAGALAA) promoted helix dimerization in POPC/cholesterol bilayers, but not without cholesterol. The predicted dimer structures and degrees of helix packing suggested that helix dimers with small (~10°) and large (~55°) crossing angles were only stabilized in POPC and POPC/cholesterol membranes, respectively. A steric hindrance in the dimer interface and the large flexibility of helices prevented the formation of stable dimers. Therefore, amino acid sequences and lipid compositions distinctively constrain stable dimer structures in membranes.

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Interactions between the Nicotinic and Endocannabinoid Receptors at the Plasma Membrane

Vallés

Barrantes

2022

Membranes

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Compartmentalization, together with transbilayer and lateral asymmetries, provide the structural foundation for functional specializations at the cell surface, including the active role of the lipid microenvironment in the modulation of membrane-bound proteins. The chemical synapse, the site where neurotransmitter-coded signals are decoded by neurotransmitter receptors, adds another layer of complexity to the plasma membrane architectural intricacy, mainly due to the need to accommodate a sizeable number of molecules in a minute subcellular compartment with dimensions barely reaching the micrometer. In this review, we discuss how nature has developed suitable adjustments to accommodate different types of membrane-bound receptors and scaffolding proteins via membrane microdomains, and how this “effort-sharing” mechanism has evolved to optimize crosstalk, separation, or coupling, where/when appropriate. We focus on a fast ligand-gated neurotransmitter receptor, the nicotinic acetylcholine receptor, and a second-messenger G-protein coupled receptor, the cannabinoid receptor, as a paradigmatic example.

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Effects of Membrane Cholesterol on Stability of Transmembrane Helix Associations

Cited by 3 publications

References 43 publications

Anticancer Activity of Methyl Protodioscin against Prostate Cancer by Modulation of Cholesterol-Associated MAPK Signaling Pathway <i>via</i> FOXO1 Induction

Anticancer Activity of Methyl Protodioscin against Prostate Cancer by Modulation of Cholesterol-Associated MAPK Signaling Pathway <i>via</i> FOXO1 Induction

Effects of Gly Residue and Cholesterol on the GXXXG‐Mediated Parallel Association of Transmembrane Helices: A Single‐Pair FRET Study

Interactions between the Nicotinic and Endocannabinoid Receptors at the Plasma Membrane

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