Review
Cell Biology
Lei Chen, Zhen-Wang Zhao, Peng-Hui Zeng, Ying-Jie Zhou, Wen-Jun Yin
Summary: The maintenance of cellular cholesterol homeostasis is crucial for normal cell function and viability. Excessive cholesterol accumulation is the molecular basis of many diseases. Peripheral cells eliminate excessive cholesterol through cholesterol efflux, which is mainly mediated by ATP-binding cassette transporter A1 (ABCA1). This article focuses on the mechanisms underlying ABCA1-mediated cholesterol efflux, providing important insights for future investigation and lipid-lowering therapy.
Article
Pharmacology & Pharmacy
Cheng Zhang, Xuewen Wu, Pengmin Shi, Hongyu Ma, Fei Fang, Qianlang Feng, Shuang Zhao, Ruipu Zhang, Jinyuan Huang, Xinting Xu, Weilie Xiao, Guang Cao, Xu Ji
Summary: In this study, it was found that diterpenoids from the traditional Chinese medicine Callicarpa rubella could effectively inhibit oxidized low-density lipoprotein-induced macrophage foam cell formation by promoting cholesterol efflux, suggesting their potential as drugs for the treatment of atherosclerosis.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Jere P. Segrest, Chongren Tang, Hyun D. Song, Martin K. Jones, W. Sean Davidson, Stephen G. Aller, Jay W. Heinecke
Summary: By using simulations, the authors of this study uncover the mechanism by which ATP-binding cassette transporter A1 (ABCA1) functions in extracting lipids from the outer face of the plasma membrane and facilitating the production of high density lipoprotein (HDL). Contrary to existing models, their findings suggest that ABCA1 removes lipids from the plasma membrane and forces them through its gateway and annulus into an elongated hydrophobic tunnel. This study provides important insights into the function of ABCA1 and presents a potential target for further research.
NATURE COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Yingying Zhang, Yongchun Liu, Yonggang Liu, Ping Zuo, Shuting Miao, Bowen Hu, Yu Kang, Wei Liu, Qingmin Yang, Hao Ren, Peng Yang
Summary: Proteins can form robust bioadhesive materials through an α-helix-mediated interfacial adhesion model. Reduction of disulfide bonds in proteins leads to the gathering of α-helices at the solid/liquid interface, exposing hydrophobic residues and disrupting the hydration layer. This model provides a unique strategy for preparing protein nanofilms with well-defined layering, exhibiting strong adhesion and resistance to various conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Medical Laboratory Technology
Shun Zhang, Lu Li, Jie Wang, Tingting Zhang, Ting Ye, Shuai Wang, Dongming Xing, Wujun Chen
Summary: lncRNAs, as a unique group of RNA transcripts longer than 200 nucleotides, regulate the roles of ABCA1 and ABCG1 in cholesterol efflux, influencing the development of atherosclerosis.
CLINICA CHIMICA ACTA
(2021)
Article
Endocrinology & Metabolism
Junlin Zhang, Jie Zhang, Rui Zhang, Yiting Wang, Fang Liu
Summary: This study investigated the effects of glomerular cholesterol accumulation due to ABCA1 deficiency on glomerular endothelial injury in diabetic kidney disease (DKD). The results showed that ABCA1 deficiency exacerbated renal lipid deposition and kidney injuries in type 2 diabetic mice. In vitro experiments also revealed that ABCA1 deficiency increased cellular cholesterol deposition, inflammation, apoptosis, and induced endoplasmic reticulum stress (ERS).
METABOLISM-CLINICAL AND EXPERIMENTAL
(2023)
Review
Medical Laboratory Technology
Wujun Chen, Lu Li, Jie Wang, Renshuai Zhang, Tingting Zhang, Yudong Wu, Shuai Wang, Dongming Xing
Summary: ABCA1 plays a central role in connecting cholesterol efflux and apoptotic cell clearance by regulating the release and expression of various ligands to promote efferocytosis.
CLINICA CHIMICA ACTA
(2021)
Article
Biochemistry & Molecular Biology
Xiao-Dan Xia, Xiao-Hua Yu, Ling-Yan Chen, Song-lin Xie, Yao-Guang Feng, Rui-Zhe Yang, Zhen-Wang Zhao, Heng Li, Gang Wang, Chao-Ke Tang
Summary: The study found that both MYOCD and ABCA1 expression were significantly decreased in atherosclerotic patient aortas. Knockdown of MYOCD inhibited ABCA1 expression in human aortic vascular smooth muscle cells (HAVSMCs), leading to reduced cholesterol efflux and increased intracellular cholesterol contents.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Biochemistry & Molecular Biology
Monoranjan Boro, Suresh Govatati, Raj Kumar, Nikhlesh K. Singh, Prahalathan Pichavaram, James G. Traylor, A. Wayne Orr, Gadiparthi N. Rao
Summary: This study revealed the mechanism of thrombin-induced depletion of ABCA1 levels, showing that CSN3 plays a crucial role in protecting ABCA1 from degradation, thus promoting cholesterol efflux and suppressing foam cell formation. Depletion of CSN3 levels in WD-fed ApoE(-/-)mice significantly lowered ABCA1 levels and exacerbated atherosclerotic plaque formation, highlighting the potential anti-atherogenic role of CSN3.
CELL DEATH AND DIFFERENTIATION
(2021)
Review
Pharmacology & Pharmacy
Masatsune Ogura
Summary: Homozygotes with loss-of-function mutations in ABCA1 develop Tangier disease, which is characterized by significantly reduced or absent blood high-density lipoprotein (HDL) cholesterol. ABCA1 was identified as a key player in HDL production based on studies involving ABCA1-deficient mice. While the activation of ABCA1 and promotion of cholesterol efflux could potentially lead to the development of anti-atherosclerotic drugs, it is challenging to consider simple ABCA1 activation or cholesterol efflux promotion as an effective strategy for intracellular cholesterol homeostasis. Currently, there is no evidence supporting the preventive effect of HDL-increasing drugs that enhance ABCA1 expression on atherosclerotic disease in humans. However, in situations where intracellular cholesterol homeostasis is disrupted by inflammation, aging, or metabolic abnormalities, restoring ABCA1 expression and cholesterol efflux may be a useful strategy.
JOURNAL OF PHARMACOLOGICAL SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jean-Baptiste Nyandwi, Young Shin Ko, Hana Jin, Seung Pil Yun, Sang Won Park, Hye Jung Kim
Summary: RA effectively promotes cholesterol efflux in macrophages by enhancing ABC transporter expression, potentially serving as a candidate therapeutic for preventing atherosclerotic cardiovascular disease complications related to diabetes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Wei-Hua Tan, Zheng-Liang Peng, Ting You, Zhi-Lu Sun
Summary: The study demonstrated that CTRP15 inhibits the development of atherosclerosis by enhancing RCT efficiency and increasing plasma HDL-C levels through the T-cadherin/miR-101-3p/ABCA1 pathway. Targeting CTRP15 may serve as a novel and promising therapeutic strategy for atherosclerotic cardiovascular diseases.
JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Review
Immunology
Wujun Chen, Shuai Wang, Dongming Xing
Summary: APE1/Ref-1 and ABCA1 play crucial roles in the progression of atherosclerosis, with APE1/Ref-1 suppressing athero-sclerosis via multiple mechanisms and ABCA1 promoting cholesterol efflux and anti-inflammatory responses. Both proteins could be potential therapeutic targets for atherosclerosis treatment.
JOURNAL OF INFLAMMATION RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Hani Dakroub, Maxime Nowak, Jean-Francois Benoist, Benoit Noel, Benoit Vedie, Jean-Louis Paul, Natalie Fournier
Summary: Incorporation of EPA into cell membranes enhances ABCA1 functionality in macrophages, leading to increased cholesterol efflux and potentially contributing to the cardioprotective effect of an EPA-rich diet highlighted in recent clinical trials.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
(2021)
Article
Pharmacology & Pharmacy
Yubing Dong, Yi Lin, Wanyu Liu, Wei Zhang, Yinong Jiang, Wei Song
Summary: The study investigated the lipid profile in hypertensive disorders of pregnancy (HDP) patients, finding significantly altered levels of plasma triglycerides, total cholesterol, LDL-C, and HDL-C compared to normotensive controls. ANP was shown to inhibit ABCA1 and ABCG1 expression at both mRNA and protein levels, leading to impaired cholesterol efflux, possibly explaining the decreased HDL-C levels in HDP patients.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Yusuke Okamoto, Maiko Tomioka, Fumihiko Ogasawara, Kota Nagaiwa, Yasuhisa Kimura, Noriyuki Kioka, Kazumitsu Ueda
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Ryota Futamata, Fumihiko Ogasawara, Takafumi Ichikawa, Atsushi Kodan, Yasuhisa Kimura, Noriyuki Kioka, Kazumitsu Ueda
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Takuma Kishimoto, Nario Tomishige, Motohide Murate, Reiko Ishitsuka, Hubert Schaller, Yves Mely, Kazumitsu Ueda, Toshihide Kobayashi
Article
Biochemistry & Molecular Biology
Fumihiko Ogasawara, Atsushi Kodan, Kazumitsu Ueda
Review
Biochemistry & Molecular Biology
Atsushi Kodan, Ryota Futamata, Yasuhisa Kimura, Noriyuki Kioka, Toru Nakatsu, Hiroaki Kato, Kazumitsu Ueda
Summary: ABCB1, also known as MDR1 or P-glycoprotein, plays a crucial role in exporting various hydrophobic compounds and serving as a protective physiological barrier in several organs. The mechanism involves an aromatic hydrophobic network triggering a conformational change in ABCB1, leading to a twist-and-squeeze motion that exports hydrophobic substrates directly to the extracellular space, distinct from other transporters.
Article
Biochemistry & Molecular Biology
Fumihiko Ogasawara, Kazumitsu Ueda
Summary: Cholesterol is a major component of the cell plasma membrane and its balance is essential for cellular functions. This study reveals that ABCA1 and Aster-A play important roles in maintaining the asymmetrical distribution of cholesterol in the plasma membrane. ABCA1 translocates cholesterol from the inner leaflet to the outer leaflet of the plasma membrane to maintain a low inner leaflet cholesterol level. When the cholesterol level increases, Aster-A is recruited to transfer cholesterol to the endoplasmic reticulum. These findings provide insights into the regulation of intracellular cholesterol homeostasis.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Multidisciplinary Sciences
Ryota Futamata, Masato Kinoshita, Katsueki Ogiwara, Noriyuki Kioka, Kazumitsu Ueda
Summary: In this study, the researchers found that ABCA1 deficiency in the Japanese medaka fish inhibits successful ovulation through cholesterol accumulation in the ovarian follicle. ABCA1A in the theca cells regulates cholesterol content in the ovarian follicles.
Article
Biochemistry & Molecular Biology
Mitsuhiro Nakato, Naoko Shiranaga, Maiko Tomioka, Hitomi Watanabe, Junko Kurisu, Mineko Kengaku, Naoko Komura, Hiromune Ando, Yasuhisa Kimura, Noriyuki Kioka, Kazumitsu Ueda
Summary: Mutations in the ABCA13 gene may increase susceptibility to psychiatric disorders. The protein encoded by this gene accelerates cholesterol internalization in neurons, which is associated with the pathophysiology of psychiatric disorders.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Kyoko Takata, Tsuyoshi Goto, Mito Kuroda, Yasuhisa Kimura, Ichiro Harada, Kazumitsu Ueda, Teruo Kawada, Noriyuki Kioka
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2020)