3‐Nitropropionic Acid Inhibition of Succinate Dehydrogenase (Complex II) Activity in Cultured Chinese Hamster Ovary Cells

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Abstract
Abstract:3‐Nitropropionic acid (3‐NPA) is an inhibitor of the mitochondrial enzyme succinate dehydrogenase (SDH, a part of complex II) that links the tricarboxylic acid (TCA) cycle to the respiratory electron transport chain. 3‐NPA inactivates SDH by covalently and irreversibly binding to its active site. We previously examined the effects of 3‐NPA on the histochemical activity of SDHin vivo,by using the reduction of a yellow tetrazolium dye (nitro blue tetrazolium) to a blue formazan as an indicator. In studies of cultured cells, the related dye methylthiazoletetrazolium (MTT) has commonly been used as an indicator of the presence and number of viable cells; that is cells that are capable of producing energy via the TCA cycle. Here we observed that doses of 3‐NPA as low as 10−8M inhibited formazan production in anin vitromodel system using CHO cells. This effect was antagonized by l‐carnitine, which greatly increased the production of formazan, indicating a considerable improvement in energy production by the cultured cells. CHO cells appear to be a convenient model for the evaluation of therapeutic compounds that may modulate cellular bioenergetics.