Vitamin E and macrophage cyclooxygenase regulation in the aged.
Aging is associated with increased evidence of cardiovascular disease (CVD). Atherosclerosis, a major cause of CVD, is an inflammatory process whose development is influenced by several proinflammatory mediators. Products of arachidonic acid metabolism, in particular, prostaglandin (PG) E(2) and thromboxane (TX) A(2), play an important role in the development of atherosclerosis. We showed previously that the aged have higher PGE(2) production compared with their young counterparts. This age-associated increase in PGE(2) production is mainly a consequence of increased cyclooxygenase (COX) activity. We demonstrated further that increased COX activity in old mice is due to the increased expression of mRNA and protein for the inducible form of COX, COX-2. Vitamin E has been shown to reduce PGE(2) production and risk of CVD. In aged mice, we showed that a vitamin E-induced decrease in PGE(2) production is due to decreased COX activity. However, vitamin E had no effect on COX mRNA and protein levels, indicating a post-translational regulation of COX by vitamin E. Further experiments indicated that vitamin E decreases COX activity through reducing formation of peroxynitrite, a hydroperoxide shown to be involved in the activation of COX-2. Other homologues of tocopherols were also effective in inhibiting COX activity, but their degree of inhibition varied. The varied potency to inhibit COX activity was not explained totally by differences in their antioxidant capacity. Vitamin E-induced inhibition of COX activity might contribute to its effect of reducing CVD risk.
Wu
D
D
Nutritional Immunology Laboratory, Jean Mayer Human Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Hayek
M G
MG
Meydani
S
S
D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000517:prevention & control; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology*; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000502:physiology; D014810:Vitamin E / Q000494:pharmacology*
D012333:RNA, Messenger; D014810:Vitamin E; D016718:Arachidonic Acid; D011451:Prostaglandin-Endoperoxide Synthases