| First Author | Chinnici CM | Year | 2005 |
| Journal | Am J Pathol | Volume | 167 |
| Issue | 5 | Pages | 1371-7 |
| PubMed ID | 16251421 | Mgi Jnum | J:102399 |
| Mgi Id | MGI:3607460 | Doi | 10.1016/S0002-9440(10)61224-2 |
| Citation | Chinnici CM, et al. (2005) Absence of 12/15 lipoxygenase reduces brain oxidative stress in apolipoprotein e-deficient mice. Am J Pathol 167(5):1371-7 |
| abstractText | The enzyme 12/15 lipoxygenase (12/15LO) has been implicated in the oxidative modification of lipoproteins and phospholipids in vivo. In addition, mice deficient in apolipoprotein E (ApoE(-/-)) are characterized by spontaneous hypercholesterolemia and a systemic increase in oxidative stress. Whereas the absence of 12/15LO reduces lipid peroxidation in the plasma and urine of ApoE(-/-) mice, the relative contribution of this enzyme to oxidative stress in the central nervous system remains unknown. Here, we provide the first in vivo evidence that 12/15LO modulates brain oxidative stress reactions using ApoE(-/-) mice crossbred with 12/15LO-deficient (12/15LO(-/-)) mice (12/15LO(-/-)/ApoE(-/-)). In chow-fed 12-month-old 12/15LO(-/-)/ApoE(-/-) mice, the amount of brain isoprostane iPF(2alpha)-VI, a marker of lipid peroxidation, and carbonyls, markers of protein oxidation, were significantly reduced when com-pared with 12/15LO-expressing controls (12/15LO(+/+)/ApoE(-/-)). These results were observed despite the fact that cholesterol, triglyceride, and lipoprotein levels were similar to those of ApoE(-/-) mice. These data indicate a functional role for 12/15LO in the modulation of oxidative reactions in the central nervous system, supporting the hypothesis that inhibition of this enzymatic pathway may be a novel therapeutic target in clinical settings involving increased brain oxidative stress. |
