The effect of cysteine-reactive catechol antioxidants on alcohol dehydrogenase as a model for oxidative stress in neurodegenerative disease

Smith, Rachel

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The effect of cysteine-reactive catechol antioxidants on alcohol dehydrogenase as a model for oxidative stress in neurodegenerative disease

Smith, Rachel

Abstract

The cellular mechanisms underlying age-related neurodegeneration, especially in disease states, are poorly understood. Oxidative stress has been heavily implicated as one factor both produced by and contributing to the progression of neurodegenerative diseases such as Alzheimer’s disease. In particular, it can destroy a cell’s ability to produce energy through aerobic and anaerobic respiration, thus leading to the death of individual cells and brain tissues as a whole. This study focuses on the relationship between oxidative stress and energy production in disease states. In particular, we examine the ability of catechol molecules to take on pro-oxidative properties and modify the enzyme alcohol dehydrogenase (ADH), both in vitro and in a yeast cellular model. Using enzyme kinetic assays, we found that when oxidized, certain catechols are able to inhibit isolated ADH activity. Though this result was not clearly replicated in vivo in yeast cellular models, we speculate that this is due to the complexity and adaptive abilities of a living system. Furthermore, native gel electrophoresis demonstrated that treatment with catechols does not induce detectable conformational change in ADH. These results suggest that oxidized catechols are able to inhibit ADH activity, but living cells may be able to adapt to the presence of these exogenous molecules through alteration of gene and protein expression. Further studies utilizing yeast cell lysis and fluorescence techniques are required to definitively ascertain antioxidant molecules’ effects on the proteins in living cells. These results have implications for the role of oxidative stress in age-related neurodegenerative disease in relation to impact on energy production.