Digitized Honors Theses (2002-2017)

Date of Award

5-2003

Document Type

Thesis

Degree Name

BS

Department

Biological Science

Faculty Mentor

Anthony Gard

Abstract

Central nervous system (CNS) cell types, in particular neurons and oligodendrocytes, are vulnerable to peroxidation of membrane lipids, a consequence of oxidative stress. This is postulated to underlie cytotoxicity associated with ischemic brain injury and the pathophysiology of many age-associated neurodegenerative diseases. The mitochondrial form of phospholipid hydroperoxide glutathione peroxidase (PHGPx) can protect non-neural cells against membrane lipid peroxidation (MLP) by directly reducing both phospholipid- and cholesterol-hydroperoxides in plasma membranes. The present study describes for the first time the expression of PHGPx in different CNS cell types. Ribonuclease Protection Assay, Northern blot, and Western blot analyses were conducted with cell type-specific primary cultures derived from neonatal rat brain to demonstrate expression of PHGPx mRNA and protein in all tested cell types, including oligodendrocytes, astrocytes, microglia, and cerebellar granule cells. Under these conditions, steady state levels of PHGPx mRNA were highest in astrocytes and granule cells. In oligodendrocyte lineage cells, PHGPx mRNA levels approximately doubled with terminal differentiation and were augmented further by 24 hr exposure of the differentiated cells to 10 ng/ml basic fibroblast growth factor (FGF-2). However, at the level of protein expression, differentiated oligodendrocytes and their counterparts treated with FGF-2 exhibited the highest level of PHGPx among cell types, increasing to >4-fold over undifferentiated oligodendrocyte progenitor cells. These data suggest that PHGPx is instrumental to cytoprotection against MLP injury in the CNS. Furthermore, these findings imply that PHGPx plays a greater role in differentiated, myelinogenic oligodendrocytes than their progenitor cells. This raises the possibility that low levels of PHGPx expression in the latter contribute to the selective vulnerability of oligodendrocyte progenitor cells to oxidative damage.

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