Premium
3‐Nitropropionic Acid Inhibition of Succinate Dehydrogenase (Complex II) Activity in Cultured Chinese Hamster Ovary Cells
Author(s) -
SCALLET ANDREW C.,
HALEY RANEY L.,
SCALLET DORI M.,
DUHART HELEN M.,
BINIENDA ZBIGNIEW K.
Publication year - 2003
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2003.tb07538.x
Subject(s) - chinese hamster ovary cell , succinate dehydrogenase , ovary , chemistry , hamster , enzyme , biochemistry , microbiology and biotechnology , biology , endocrinology , receptor
A bstract : 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.