Increased expression of glyceraldehyde-3-phosphate dehydrogenase in cultured astrocytes following exposure to manganese

Manganism is a disorder characterized by hyperintensities in basal ganglia structures on magnetic resonance imaging which may be the consequence of ma nganese deposition in these areas. Since manganese is taken up avidly into astrocytes and is known to interfere with cerebral energy metabolism, we st udied the effect of this metal on the expression and activity of the glycol ytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in primary cul tures of astrocytes. Treatment with 100 mu M manganese for 7 days increased both the V-max and K-m values for GAPDH which was not reproducible with ot her divalent metals. Using RT-PCR, increased GAPDH expression was detected in cells exposed to manganese compared with controls. No changes in cytochr ome oxidase activity or ATP levels were observed, and lactate production wa s unaffected, in manganese-treated cells. These findings provide evidence o f a possible role for GAPDH in the mediation of the effects of manganese on central nervous system function. (C) 1999 Elsevier Science Ltd. All rights reserved.