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Ann N Y Acad Sci ; 993: 305-12; discussion 345-9, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12853322

RESUMO

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 SDH in 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(-8) M inhibited formazan production in an in vitro model 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.


Assuntos
Carnitina/farmacologia , Propionatos/farmacologia , Succinato Desidrogenase/antagonistas & inibidores , Animais , Células CHO , Carnitina/metabolismo , Respiração Celular/efeitos dos fármacos , Corantes/metabolismo , Cricetinae , Inibidores Enzimáticos/farmacologia , Formazans/metabolismo , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Nitrocompostos , Oxirredução , Propionatos/metabolismo , Succinato Desidrogenase/metabolismo , Sais de Tetrazólio/metabolismo , Tiazóis/metabolismo
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