|
KMID : 0385219910010020187
|
|
Korean Journal of Gerontology
1991 Volume.1 No. 2 p.187 ~ p.201
|
|
|
Oxidative Stress and Age-Related Changes in Microsomal Mixed Function Oxidase Activity
|
|
|
|
|
Abstract
|
|
|
|
Age-dependent decline in the function of hepatic microsomal mixed function oxidase system (MFOS) has been observed human and laboratory animals. Such as age-related alteration of MFOS may be resulted from a number of factors, including a loss of smooth endoplasmic reticulum or MFOS constituents, alteration in the quality of MFOS enzymes or heme proteins, changes in the lipid microenvironment of MFOS, and any of combination of the above. Current studies have indicated that an inclusive deterioration in function of MFOS is closely related to the status of in vivo oxidative stress rather than the change in expression of major enzymes responsible for MFOS activity. We provided further evidence supporting this hypothesis. Namely, microsomal cytochrome P-450, a central enzyme of MFOS, was rapidly destroyed by oxidative stress regardless of its induction system, and cytochrome P-450 degradation seems to be due to direct action of some by-products of lipid peroxidation on the substrate binding site of this enzyme. We obtained very interesting results from ad libitum and food restricted rats with age. The contents of cytochrome P-450 and its related enzyme activities were declined with age, and more degradation of cytochrome P-450 by oxidative stress was shown in ad libitum rats than food restriction one. However the cytosolic protective capacity against cytochrome P-450 destruction was enhanced by food restriction. There results indicated that food restriction enhances the stability of the microsomal membranes against lipid peroxidation and free radical damage, and provides an optimal structural environment for the activity of MFOS. In this review, it will be discussed on the specific functions of cytochrome P-450, generation of reactive oxygen species by cytochrome P-450, oxidative damage of MFOS components, interrelationships between lipid peroxidation and MFO activity, and effect of dietary restriction on MFOS.
|
|
|
KEYWORD
|
|
|
Mixed function oxidase, Cytochrome P-450, Lipid peroxidation, Aging, oxygen free radicals, Food restriction
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|
|