Thiamine Metabolism in Neurons and Their Vital Capacity Upon the Action of Ethanol and Acetaldehyde

We studied the sensitivity of a few reactions of thiamine metabolism in nerve cells upon the action of ethanol and acetaldehyde, as well as effects of the above-mentioned agents on vital capacity of cultured cells of different origins. Experiments were carried out on preparations of isolated nerve endings (synaptosomes), preparations of synaptosomal plasma membranes (SPMs), preparations of enzymes, and cell cultures. We estimated the ІС50 for the effects of ethanol and acetaldehyde on reactions that are the components of metabolism of the mobile thiamine pool in the cells. Ethanol in physiological concentrations inhibited the thiamine-binding activity of SPMs (ІС50 = 3.9 mM). At the same time, this agent used in the above concentrations practically did not influence the thiamine phosphate hydrolase activity of SPMs (estimated by the thiamine triphosphatase activity) and thiamine pyrophosphate kinase (TPK) activity. A product of ethanol metabolism, acetaldehyde, inhibited the thiamine triphosphatase activity with Kі = 6.2 μM and the TPK activity with Kі = 1.2 μM. The survival indices of cultured cells were estimated under conditions of the addition of ethanol and acetaldehyde to the medium. The cells of an astrocytic origin (line strain 1321 N1) and blood cells (line strain U937) practically did not respond to the presence of ethanol or acetaldehyde even in rather high concentrations in the culture medium. Under conditions of primary culture, neuron-like (differentiated) cultured РС-12 cells and also cerebellar granular neurons responded by significant decreases in the index of vital capacity to the addition of the above agents.