Distribution of glutathione and glutathione-related enzyme systems in mitochondria and cytosol of cultured cerebellar astrocytes and granule cells

The cellular and regional distribution of glutathione (GSH) and GSH-related enzyme systems involved in cellular defense against reactive oxygen species and electrophilic xenobiotics in the nervous system has been extensively studied. However, little is known about the subcellular distribution of GSH systems in brain tissue and cultured neural cells. The present study investigates the distribution of mitochondrial and cytosolic GSH and GSH-related enzymes in cultured cerebellar astrocytes and granule cells, and compares them with levels in the adult rat cerebellum. Cytosolic GSH levels and cytosolic activities of glutathione reductase (GR), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in astrocytes were 57, 153, 245, and 92% higher than those found in granule cells, respectively. In contrast, granule cells contained significantly higher mitochondrial GSH levels than astrocytes. Granule cells also demonstrated comparable mitochondria/cytosolic concentrations of GSH and GR, GPX and GST activities to those observed in the cerebellar tissue, whereas ratios in astrocytes were markedly lower. Although in vitro treatments with 100 μM ethacrynic acid depleted both cytosolic and mitochondrial GSH in cultured astrocytes and granule cells in a time-dependent fashion, cellular GSH in granule cells was more resistant to the GSH-depleting agent than astrocytes. These results suggest that although GSH and GSH-related enzymes are abundant in cytosolic compartments of astrocytes, mitochondrial pools are relatively small. Since brain mitochondria are sites of significant hydrogen peroxide generation, the mitochondrial localization of GSH and its associated enzymes in neural cells provide important defenses against toxic oxygen species in the nervous system. Differences in subcellular distribution of GSH systems in individual neural cell types may provide a basis for selective cellular and/or subcellular expression of neurotoxicity.     

Nutrition, Exercise, and Healthy Aging

Advancing age is associated with a remarkable number of changes in body composition, including reduction in lean body mass and increase in body fat, which have been well documented. Decreased lean body mass occurs primarily as a result of losses in skeletal muscle mass. This age-related loss in muscle mass has been termed “sarcopenia”. Loss in muscle mass accounts for the age-associated decreases in basal metabolic rate, muscle strength, and activity levels, which, in turn are the cause of the decreased energy requirements of the elderly. In sedentary persons, the main determinant of energy expenditure is fat-free mass, which declines by about 15% between the third and eighth decade of life. It also appears that declining energy needs are not matched by an appropriate decline in energy intake, with the ultimate result being increased body fat content. Increased body fatness and increased abdominal obesity are thought to be directly linked to the greatly increased incidence of non-insulin-dependent diabetes mellitus among the elderly. In this review we will discuss the extent to which regularly performed exercise can affect nutrition needs and functional capacity in the elderly. We will also discuss a variety of concerns when prescribing exercise in the elderly, such as planning for a wide variability in functional status, medical status, and training intensity and duration. Finally, we will attempt to provide some basic guidelines for beginning an exercise program for older men and women and establishing community-based programs.     

Genetics: Changing Health Care in the 21st Century

Advances in human genetics are rapidly changing the scope of information and care that can be provided to health care consumers. By the year 2005 it is expected that the entire human genome will be mapped and all 70,000–100,000 genes will be identified. Currently, there are more than 5,000 known single-gene disorders. With the movement of specialized health services into the primary care setting, nurses increasingly will need to be knowledgeable about genetic disorders, screening/diagnostic tests, and implications for health care. In addition, the management of genetic information raises issues of informed consent, privacy and confidentiality, truth telling and disclosure, and nondiscrimination.