Chapter 7 Gene induction, protein synthesis, and related issues

Publisher Summary This chapter outlines the role of genes in ischemia and stroke. Stroke is a leading cause of adult disability. Every stroke sets in motion a neuroprotective response by the brain to counteract the damaging effects of reduced flow. These events are mediated by alterations of molecular transcription and translation. Both these fundamental processes are affected by ischemia. The multifaceted cascade of physiological and biochemical events triggered by ischemia is mediated by alterations of molecular transcriptional and translational activities. DNA microarray technology allows detection and quantification of the differential expression of thousands of genes simultaneously in a single experiment. This technology is now being extended to many research areas, including studies of cerebral ischemia. One difficulty in evaluating results obtained by microarray is that this technique may not detect genes with low expression levels. The massive suppression of protein synthesis that follows cerebral ischemia is another factor to consider in the interpretation of microarray studies. As unfolded proteins accumulate in the lumen of the endoplasmic reticulum, the initial response is directed at reducing the number of newly translated proteins entering the endoplasmic reticulum and increasing the capacity of the cell to process proteins. Epidemiological studies have identified several major modifiable risk factors for stroke, such as obesity, diabetes, hypertension, smoking, sedentary lifestyle, hypertriglyceridemia, and hypercholesterolemia. Cohort studies are identifying genetic susceptibilities in certain families with higher stroke incidence.