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Antioxidant Protection Mechanisms And Arachidonic Acid Synthesis Are Altered In Schwann Cells Grown In Elevated Glucose
Author(s) -
Miinea C,
Eichberg J.
Publication year - 2000
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2000abstracts-34.x
Subject(s) - arachidonic acid , catalase , phosphatidylethanolamine , superoxide dismutase , glutathione , phospholipid , biochemistry , oxidative stress , antioxidant , chemistry , linoleic acid , phosphatidylcholine , endocrinology , medicine , fatty acid , biology , enzyme , membrane
Accumulating evidence points to oxidative stress as an important factor in the onset of diabetic neuropathy. We have investigated the status of antioxidant protection mechanisms in immortalized rat Schwann cells cultured in high (30 and 50 mM) concentrations of glucose. As compared to growth in 5 mM glucose, the cells contained 40% less reduced glutathione (n =8, p < 0.01). Total superoxide dismutase activity was diminished by more than 50% (n=3; p < 0.001), whereas catalase activity was unchanged. The cellular NADH/NAD + ratio was progressively increased with increasing medium glucose concentrations. Our previous findings have established that upon exposure of cultured cells to elevated glucose, the proportions of arachidonic acid‐containing molecular species (ACMS) in phospholipids are decreased in a pattern similar to alterations exhibited by diabetic nerve. To examine whether biosynthesis of arachidonic acid might be perturbed, confluent cells maintained in either high or low glucose were incubated with either [ 14 C]linoleic acid (18:2) or [ 14 C]dihomo‐γ‐linolenic acid (20:3) and radioactivity incorporated into molecular species of major phospholipid classes was measured. The incorporation of 18:2 either as unchanged fatty acid or into ACMS did not differ as a function of glucose concentration. Negligible labeled 18:3 or 20:3 molecular species were detected. In contrast, the uptake of 20:3 into 18:1/20:4 and 16:0/20:4 phosphatidylcholine and 18:1/20:4 phosphatidylethanolamine, but not into 20:3‐containing molecular species, was significantly reduced in cells cultured in 30 mM glucose. These data imply that Δ5 desaturase activity is decreased in cells exposed to elevated glucose. This reduced enzyme activity could adversely affect polyunsaturated fatty acid metabolism and might arise as a consequence of impaired scavenging of reactive oxygen species. (Supported by NIH grant DK30577)