| RRC ID |
64451
|
| 著者 |
Ninomiya R, Kubo S, Baba T, Kajiwara T, Tokunaga A, Nabeka H, Doihara T, Shimokawa T, Matsuda S, Murakami K, Aigaki T, Yamaoka Y, Hamada F.
|
| タイトル |
Inhibition of low-density lipoprotein uptake by Helicobacter pylori virulence factor CagA.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Helicobacter pylori (H. pylori) infection mainly causes gastroduodenal diseases, including chronic gastritis, peptic ulcer disease and gastric cancer. In recent years, several studies have demonstrated that infection with H. pylori, especially strains harboring the virulence factor CagA (cytotoxin-associated gene A), contribute to the development of non-gastric systemic diseases, including hypercholesterolemia and atherosclerotic cardiovascular diseases. However, mechanisms underlying this association has not been defined. In this study, we carried out a large-scale genetic screen using Drosophila and identified a novel CagA target low-density lipoprotein receptor (LDLR), which aids in the clearance of circulating LDL. We showed that CagA physically interacted with LDLR via its carboxy-terminal region and inhibited LDLR-mediated LDL uptake into cells. Since deficiency of LDLR-mediated LDL uptake has been known to increase plasma LDL and accelerate atherosclerosis, our findings may provide a novel mechanism for the association between infection with CagA-positive H. pylori and hypercholesterolemia leading to atherosclerotic cardiovascular diseases.
|
| 巻・号 |
556
|
| ページ |
192-198
|
| 公開日 |
2021-6-4
|
| DOI |
10.1016/j.bbrc.2021.03.170
|
| PII |
S0006-291X(21)00582-9
|
| PMID |
33845309
|
| MeSH |
Animals
Animals, Genetically Modified
Antigens, Bacterial / metabolism*
Atherosclerosis / microbiology
Bacterial Proteins / metabolism*
Drosophila melanogaster / anatomy & histology
Drosophila melanogaster / genetics
Drosophila melanogaster / metabolism
Eye / metabolism
Female
Helicobacter pylori / metabolism*
Helicobacter pylori / pathogenicity*
Humans
Hypercholesterolemia / microbiology
Lipoproteins, LDL / blood
Lipoproteins, LDL / metabolism*
Male
Protein Binding
Receptors, LDL / metabolism*
Virulence Factors / metabolism*
|
| IF |
2.985
|
| リソース情報 |
| ショウジョウバエ |
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