Lysophosphatidic acid-induced oxidized low-density lipoprotein uptake is class A scavenger receptor-dependent in macrophages |
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| Institution: | 1. Institute of Zoology, National Taiwan University, Taipei, Taiwan, ROC;2. Department of Life Science, National Taiwan University, Taipei, Taiwan, ROC;3. Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan, ROC;4. Center for Food and Biomolecules, National Taiwan University, Taipei, Taiwan, ROC;5. Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan, ROC;1. Department of Urology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China;2. Department of Urology, The Affiliated Hospital of Chengdu University, Chengdu, China;1. Department of Gastrointestinal Surgery, Graduate School of Medicine, the University of Tokyo, Tokyo, Japan;2. Department of Gastroenterology, Tianjin Medical University Cancer Hospital, City Key Laboratory of Tianjin Cancer Center and National Clinical Research Center for Cancer, Tianjin, China;1. Pós-graduação em Medicina Veterinária, Universidade Federal Fluminense, Rua Vital Brazil Filho, 64, Santa Rosa, Niterói, RJ CEP 24230-340, Brazil;2. Unit Cytokines and Inflammation, Department of Infection & Epidemiology, 28 Rue du Docteur Roux, 75015 Paris, France;3. Laboratório de Pesquisa Clínica em Dermatozoonoses em Animais Domésticos, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ CEP 21040-360, Brazil;4. Laboratório de Vigilância em Leishmanioses, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Av. Brasil, 4365, Manguinhos, Rio de Janeiro, RJ CEP 21040-360, Brazil;5. Universidade Federal de São João del-Rei, campus Centro Oeste Dona Lindu, Rua Sebastião Gonçalves Coelho, 400, Bairro Chanadour, Divinópolis, MG CEP 35501-296, Brazil |
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| Abstract: | Lysophosphatidic acid (LPA) is a low-molecular-weight lysophospholipid enriched in platelets and mildly oxidized low-density lipoprotein (OxLDL). It is suggested that LPA is involved in atherosclerosis, and our previous studies showed that LPA regulates inflammation in multiple cell types. The main aim of this study was to investigate the effects of LPA on the uptake of OxLDL by mouse J774A.1 macrophages. We observed that LPA upregulated fluorescence-labeled DiI-OxLDL uptake in J774A.1 cells. Meanwhile, expression of the class A scavenger receptor (SR-A), a receptor for modified LDL, was also enhanced. Furthermore, pertussis toxin (PTx) or Ki16425 significantly abolished LPA's effects, indicating that Gi and LPA3 are involved in OxLDL uptake and SR-A expression. Of most importance, the LPA-induced OxLDL uptake could be inhibited when cells were incubated with a functional blocking antibody of SR-A. Our results suggest that LPA-enhanced OxLDL uptake is mediated via LPA3-Gi activation and subsequent SR-A expression. |
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