Copper stress proteins, effect

Recent publications signal the continued interest in the function of this protein. It has been called a stress enzyme, involved in influenza virus infection (Tomas and Toparceanu, 1986). An explanation for Wilson s disease in terms of a genetic defect resulting in failure to convert from a neonatal (i.e., low) level of ceruloplasmin and copper to a normal adult level has been reported (Srai et al., 1986). Tissue specificity for the binding of ceruloplasmin to membranes was demonstrated in a study investigating the possible role of ceruloplasmin-specific receptors in the transfer of copper from ceruloplasmin to other copper-containing proteins (Orena et al, 1986). Ceruloplasmin has been shown to be effective in transferring copper to Cu,Zn-SOD in culture (Dameron and Harris, 1987), as has copper albumin. In view of the variable content of copper in this protein, it is not clear which copper is transferred. 

Evidence for a stress-protective activity of PrPc was first provided by experiments with primary neurons from PrP0/0 mice [118]. Using murine stroke models it was then demonstrated that PrPc confers neuroprotection after an ischemic insult [119-123]. These findings in transgenic animals were corroborated and complemented by several studies in cultured cells, demonstrating a protective effect of PrPc against neuronal cell death induced by oxidative stress [124, 125], copper [126], protein synthesis inhibitors [127, 128], and excitotoxins [95, 96] (Fig. 1). 

Copper is essential for some of the enzymes that have a role in brain metabolism. Sophisticated mechanisms balance copper import and export to ensure proper nutrient levels (homeostasis) while minimizing toxic effects. Several neurodegenerative diseases including AD are characterized by modified copper homeostasis. This change seems to contribute either directly or indirectly to increased oxidative stress, an important factor in neuronal toxicity. The association of misfolded proteins and modified copper homeostasis appears to be important in the pathological progression of AD [Donnelly et al., 2007],... 

Several studies indicate that catechins and procyanidins are powerful scavengers of ROS. Some findings regarding the antioxidant activity of proanthocyanidins are listed in Ref. [100]. Other antioxidant mechanisms are the chelation of transition metals, as well as the mediation and inhibition of enzymes. The metal-chelating activity of proanthocyanidins is thought to be due to their capacity to reduce the concentration, and thus the oxidative activity, of hydroxyl radicals formed by Fenton reaction catalyzed by iron or copper. Flavanols also influence oxidative stress via enzyme modification and modulation of cell signaling pathways the extent of the effect relies greatly on flavanol structure-related protein reactivity [101]. 

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