| First Author | Yi X | Year | 2009 |
| Journal | J Leukoc Biol | Volume | 85 |
| Issue | 1 | Pages | 146-53 |
| PubMed ID | 18845616 | Mgi Jnum | J:143405 |
| Mgi Id | MGI:3826894 | Doi | 10.1189/jlb.0308161 |
| Citation | Yi X, et al. (2009) Mice with heterozygous deficiency of lipoic acid synthase have an increased sensitivity to lipopolysaccharide-induced tissue injury. J Leukoc Biol 85(1):146-53 |
| abstractText | alpha-Lipoic acid (1, 2-dithiolane-3-pentanoic acid; LA), synthesized in mitochondria by LA synthase (Lias), is a potent antioxidant and a cofactor for metabolic enzyme complexes. In this study, we examined the effect of genetic reduction of LA synthesis on its antioxidant and anti-inflammatory properties using a model of LPS-induced inflammation in Lias+/- mice. The increase of plasma proinflammatory cytokine, TNF-alpha, and NF-kappaB at an early phase following LPS injection was greater in Lias+/- mice compared with Lias+/+ mice. The circulating blood white blood cell (WBC) and platelet counts dropped continuously during the initial 4 h. The counts subsequently recovered partially in Lias+/+ mice, but the recovery was impaired totally in Lias+/- mice. Administration of exogenous LA normalized the recovery of WBC counts in Lias+/- mice but not platelets. Enhanced neutrophil sequestration in the livers of Lias+/- mice was associated with increased hepatocyte injury and increased gene expression of growth-related oncogene, E-selectin, and VCAM-1 in the liver and/or lung. Lias gene expression in tissues was 50% of normal expression in Lias+/- mice and reduced further by LPS treatment. Decreased Lias expression was associated with diminished hepatic LA and tissue oxidative stress. Finally, Lias+/- mice displayed enhanced mortality when exposed to LPS-induced sepsis. These data demonstrate the importance of endogenously produced LA for preventing leukocyte accumulation and tissue injury that result from LPS-induced inflammation. |
