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Niemann-Pick C1-Like 1 (NPC1L1) is a gene associated with NPC1 which mutation results in Niemann-Pick disease. It codes for Niemann-Pick C1-like protein 1, found on the gastrointestinal tract epithelial cells^[1] as well as in hepatocytes.^[2] Specifically, it appears to bind to a critical mediator of cholesterol absorption.

The drug ezetimibe blocks the NPC1L1 causing a reduction in cholesterol absorption, resulting in a blood cholesterol reduction of between 15-20%. Polymorphic variations in NPC1L1 gene could be associated with non-response to ezetimibe treatment. ^[3]

NPC1L1 has been shown to be an accessory receptor for Hepatitis C virus entry into cells, and thus ezetimibe might be used as a therapeutic strategy^[4]

External links

NPC1L1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

References

^ Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A 2005;102(23):8132-7. PMID 15928087
^ Temel, Ryan E., Tang, Weiqing, Ma, Yinyan, Rudel, Lawrence L., Willingham, Mark C., Ioannou, Yiannis A., Davies, Joanna P., Nilsson, Lisa-Mari, Yu, Liqing. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe J. Clin. Invest. 2007 0: JCI30060
^ Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human). Available from: http://www.uniprot.org/uniprot/Q9UHC9 Accessed 3 September 2012
^ Sainz, Bruno; Barretto, Naina; Martin, Danyelle N; Hiraga, Nobuhiko; Imamura, Michio; Hussain, Snawar; Marsh, Katherine A; Yu, Xuemei; Chayama, Kazuaki; Alrefai, Waddah A; Uprichard, Susan L (8 January 2012). "Identification of the Niemann-Pick C1–like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor". Nature Medicine 18 (2): 281–285. doi:10.1038/nm.2581.

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1. スタチン系およびフィブラート系以外の薬剤による脂質低下 lipid lowering with drugs other than statins and fibrates

English Journal

Relative expression of cholesterol transport-related proteins and inflammation markers through the induction of 7-ketosterol-mediated stress in Caco-2 cells.

Alemany L, Laparra JM, Barberá R, Alegría A.SourceNutrition and Food Chemistry, Faculty of Pharmacy, University of Valencia, Avda. Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.Food Chem Toxicol.2013 Jun;56:247-53. doi: 10.1016/j.fct.2013.02.040. Epub 2013 Feb 27.
Human diets contain sterol oxidation products that can induce cytotoxic effects, mainly caused by cholesterol oxides. However, phytosterol oxides effects have been less extensively investigated. This study evaluates the production of inflammatory biomarkers (IL-1β, IL-8, IL-10, TNFα) and the influ
PMID 23454145

Ezetimibe inhibits hepatic niemann-pick c1-like 1 to facilitate macrophage reverse cholesterol transport in mice.

Xie P, Jia L, Ma Y, Ou J, Miao H, Wang N, Guo F, Yazdanyar A, Jiang XC, Yu L.SourceDepartment of Animal and Avian Sciences, University of Maryland, College Park, MD 20742. lyu123@umd.edu.
Arteriosclerosis, thrombosis, and vascular biology.Arterioscler Thromb Vasc Biol.2013 May;33(5):920-5. doi: 10.1161/ATVBAHA.112.301187. Epub 2013 Mar 7.
OBJECTIVE: Controversies have arisen from recent mouse studies about the essential role of biliary sterol secretion in reverse cholesterol transport (RCT). The objective of this study was to examine the role of biliary cholesterol secretion in modulating macrophage RCT in Niemann-Pick C1-Like 1 (NPC
PMID 23471229

Characterization of Lactobacillus plantarum Lp27 isolated from Tibetan kefir grains: A potential probiotic bacterium with cholesterol-lowering effects.

Huang Y, Wu F, Wang X, Sui Y, Yang L, Wang J.SourceCentral Research Laboratory, Second Hospital of Jilin University, Changchun 130041, People's Republic of China.
Journal of dairy science.J Dairy Sci.2013 May;96(5):2816-25. doi: 10.3168/jds.2012-6371. Epub 2013 Mar 15.
Lactobacillus plantarum Lp27 was isolated from Tibetan kefir grains. The Lp27 isolate survived a 3-h incubation at pH 2.0 and grew normally in 0.3% oxgall. In addition, the Lp27 isolate exhibited an adhesion ratio of 9.5±2.5% with Caco-2 cells. Antibiotic susceptibility tests indicated that the Lp2
PMID 23498003

Japanese Journal

生活習慣病関連物質のトランスポーターによる体内動態制御に関する研究

高田龍平
YAKUGAKU ZASSHI 133(4), 451-461, 2013
Recent studies revealed the importance of transporters in the behaviors of small molecules in the body. In mammals, the presence of a lot of transporters has been suggested, such as ATP-binding cass …
NAID 130003361936

エゼチミブの使い方 (特集脂質異常症 : 動脈硬化性疾患予防のために) -- (脂質異常症の治療 : 各論)

石井秀人,吉田雅幸
診断と治療 100(12), 2051-2055, 2012-12-00
NAID 40019515713

食後高中性脂肪血症(食後高脂血症)に対するエゼチミブの効果

山下静也
循環器内科 71(5), 460-469, 2012-05-00
NAID 40019343178

Related Pictures

Cdc42 Regulates the Transport of NPC1L1 towards Plasma Membrane----Shanghai Institutes Liver enzyme may play critical role in enhancing cholesterol removal from the body Schematic diagram of the proposed mechanisms of ezetimibe-induced | Download NPC1L1: Evolution From Pharmacological Target to Physiological Sterol Transporter 降血脂能否减少心脏病发作之争论再起_亿度网 Ezetimibe: Its Novel Effects on the Prevention and the Treatment of Cholesterol Cholesterol Trafficking | Cayman Chemical

★リンクテーブル★

リンク元	「エゼチミブ」
関連記事	「NPC1L」

「エゼチミブ」

NPC1 (Niemann-Pick disease, type C1, gene)-like 1
Identifiers
Symbol	NPC1L1
Entrez	29881
HUGO	7898
OMIM	608010
RefSeq	NM_013389
UniProt	Q9UHC9
Other data
Locus	Chr. 7 p13

　　[★]

英: ezetimibe
関: ゼチーア(バイエル)
関: 高脂血症治療薬

コレステロールトランスポーター阻害薬

作用機序

Niemann-Pick C1-Like1(NPC1L1)を選択的に阻害　→　コレステロール吸収を抑制

コレステロールの吸収に関する輸送体である

「NPC1L」

　　[★]

関: Niemann-Pick Cl-like protein

[Garcia-Calvo2005-1] Garcia-Calvo M, Lisnock J, Bull HG, Hawes BE, Burnett DA, Braun MP, et al. The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1). Proc Natl Acad Sci U S A 2005;102(23):8132-7. PMID 15928087

[Temel-2] Temel, Ryan E., Tang, Weiqing, Ma, Yinyan, Rudel, Lawrence L., Willingham, Mark C., Ioannou, Yiannis A., Davies, Joanna P., Nilsson, Lisa-Mari, Yu, Liqing. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe J. Clin. Invest. 2007 0: JCI30060

[3] Niemann-Pick C1-like protein 1 precursor - Homo sapiens (Human). Available from: http://www.uniprot.org/uniprot/Q9UHC9 Accessed 3 September 2012

[4] Sainz, Bruno; Barretto, Naina; Martin, Danyelle N; Hiraga, Nobuhiko; Imamura, Michio; Hussain, Snawar; Marsh, Katherine A; Yu, Xuemei; Chayama, Kazuaki; Alrefai, Waddah A; Uprichard, Susan L (8 January 2012). "Identification of the Niemann-Pick C1–like 1 cholesterol absorption receptor as a new hepatitis C virus entry factor". Nature Medicine 18 (2): 281–285. doi:10.1038/nm.2581.

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NPC1L1