Glyceraldehyde 3-Phosphate Dehydrogenase Abnormality in Metabolically Stressed Huntington Disease Fibroblasts

Abstract

Huntington disease (HD) fibroblasts subjected to stress exhibit an enzyme profile that is different from that exhibited by escapee (unaffected members of families with HD) or control fibroblasts. The specific activity of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in normally cultured HD fibroblasts was not different from that in control and escapee fibroblasts. However, in escapee and control fibroblasts subjected to stress by withholding fresh medium, the specific activity of GAPDH in cells harvested by trypsinization increased greatly 3 weeks after withholding medium (∼8-fold), but the increase was significantly less pronounced (∼3-fold) in the HD fibroblasts. In contrast, only small changes occurred in the specific activity of lipoamide dehydrogenase (LADH) over the same time period, and the values were not significantly different among the three groups at any time point. The specific activity of hexokinase (HK) was significantly higher in the HD fibroblasts at 1–3 weeks after withholding fresh medium than in the escapee/control fibroblasts. Finally, the total yield of fibroblasts per culture flask (as judged by protein content) was significantly greater for the stressed HD fibroblasts than for the escapee and control fibroblasts at 2 and 3 weeks after withholding medium. The present results are in accord with the hypothesis that HD is a disease associated with latent, generalized metabolic abnormalities.

Glycolysis Inhibition Decreases the Levels of Glutamate Transporters and Enhances Glutamate Neurotoxicity in the R6/2 Huntington′s Disease Mice

“…However, in [41,42]. Another study reported no changes in enzyme activity during resting conditions in fibroblasts from HD patients, but under energy demanding conditions a lower activation of GAPDH was observed, as compared to that shown by fibroblasts from control individuals [43]. The present study shows no changes in basal GAPDH activity, but IOA treatment induced a larger inhibition of the enzyme in transgenic mice, particularly, in the cerebral cortex and the hippocampus.…”

Reduction of glyceraldehyde‐3‐phosphate dehydrogenase activity in Alzheimer's disease and in Huntington's disease fibroblasts

“…Specific activity was expressed as milliunit (mU)/mg protein. A milliunit was defined as the amount of enzyme required to catalyse the production of 1 nmol NADH per minute (Cooper et al . 1998).…”

Nitric oxide and neurological disorders

“…Additionally, in HD studies, GAPDH has been reported to bind and form a complex with the huntingtin protein (Burke et al, 1996;Cooper et al, 1998).…”