Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 467, Issue 1, Pages 135-139Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2015.09.100
Keywords
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1); Calpains; Macrophage migration; Oxidized low-density lipoprotein; Calcium
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Funding
- Department of Veterans Affairs, Veterans Health Administration, office of Research and Development [BX-000282-05]
- Biomedical Laboratory Research and Development, Washington, DC
- National Natural Science Foundation of China [81370428]
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Previous studies have shown that oxidized low-density lipoprotein (ox-LDL) inhibits macrophage migration, but the precise mechanisms remain unclear. Lectin-like ox-LDL receptor-1 (LOX-1) is a scavenger receptor that is expressed in macrophages and binds ox-LDL Calpains, a family of calciumdependent proteases, influence several aspects of cell migration. In this study, we investigated the role of LOX-1 in macrophage migration in response to ox-LDL and the involvement of calpains in this process. Peritoneal macrophages from wild type C57BL/6 mice were exposed to different concentrations of ox-LDL (1-20 mu g/mL), and expression of LOX-1 and calpain-1 and -2, cell migration and intracellular calcium (Ca2+ in) were measured. Our results showed that ox-LDL stimulated LOX-1 and calpain-2 expression, and inhibited calpain-1 expression in a dose- and time-dependent manner. Further, ox-LDL inhibited macrophage migration and increased Ca2+ in, concentration in macrophages. To further elucidate the role of LOX-1 in ox-LDL-impaired macrophage migration, we isolated peritoneal macrophages from LOX-1 knockout mice, and treated them with ox-LDL Interestingly, calpain-1 expression was much higher, and calpain-2 expression was lower in LOX-1 knockout macrophages than in wild-type macrophages following exposure to ox-LDL LOX-I deletion significantly improved macrophage migration and decreased Ca2+ in concentration. These data indicate that LOX-1 is, at least in part, responsible for the inhibitory effect of ox-LDL on macrophage migration and this process involves calpain-1 and -2. Published by Elsevier Inc.
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