Cytoprotective enzymes

Such a plethora of radicals produced as a result of normal cellular metabolism needs to be rapidly scavenged by cytoprotective enzymes and antioxidants present in the cell and cellular membranes, both hydrophobic and hydrophilic compartments. The... 

Figure 10.1 Ward cascade showing the cooperation between cytoprotective enzymes and antioxidants for scavenging of reactive oxygen and reactive nitrogen species.

Over the past years it has become apparent that the cell type is an important determinant of the extent of oxidative stress that may occur. Both the latent activities of cytoprotective enzymes in specific cell types, as well as the ability of the cell to respond rapidly to an oxidative insult by the upregulation of such enzymes, will be important predeterminants of the fate of the cell. Table 10.1 shows the concentrations of both antioxidants and cytoprotective enzymes in a variety of tissues. While the liver is well provided with antioxidant protection, the brain has very low levels, so the ability to respond rapidly to an oxidative insult by upregulation of gene transcription and translation will be an important determinant of survival or death. Cells such as hepatocytes have high levels of expression and... 

Table 10.1 Antioxidant and cytoprotective enzyme content in a variety of rat tissues.

Plant Phenolic Compounds Modulation of Cytoprotective Enzymes and Nrf2/ARE Signaling... 

Modulation of Cytoprotective Enzymes by Plant Phenolic Compounds Structure-Activity Relationship 408... 

INDIRECT CYTOPROTECTIVE ACTIVITY OF PLANT PHENOLIC COMPOUNDS AND CYTOPROTECTIVE ENZYMES... 

MODULATION OF CYTOPROTECTIVE ENZYMES BY PLANT PHENOLIC COMPOUNDS STRUCTURE-ACTIVITY RELATIONSHIP... 

To better understand the health effects of plant phenolic compounds and to better utilize them, it is necessary to know the molecular mechanisms by which plant phenolic compounds induce cytoprotective enzymes. In vitro studies indicated that plant phenolic compounds such as curcumin often inhibited the enzymatic activities of GST, UGT, SULT as well as cytochrome P450s [Oetari et al., 1996], suggesting that the induction of cytoprotective enzyme activities could not be explained by direct interaction with plant phenolic compounds. On the other hand, much evidence indicates that the increased activity of cytoprotective enzymes are mainly attributable to enhanced transcriptional activation and enzyme synthesis [Holtzclaw et al., 2004]. 

Further structure-activity relationship (S AR) analyses of other cytoprotective enzyme inducers revealed the fact that all inducers can react with thiol/disulfide groups by alkylation, oxidoreduction, or thiol-disulfide interchange [Dinkova-Kostova and Talalay, 1999]. In fact, the capability of enzyme inducers to induce cytoprotective enzymes is well correlated with their reactivity with thiols. These results suggested a cellular sensor of inducers with highly reactive sulfhydryl groups, possibly reactive thiols in cysteine residues of a sensor protein. Nevertheless, the initial search for the sensor protein by using radioactively labeled inducers was not successful due to the abundance of thiol groups presented in many proteins in cells [Holtzclaw et al., 2004]. The molecular mechanism by which cytoprotective enzymes are induced remained to be elucidated. 

New understanding of the mechanism underlying the induction of cytoprotective enzymes came from analysis of the DNA sequences in the 5 -flanking promoter regions of several phase 2 genes. Two sequences in the upstream... 

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