Effects of taurine and homocysteine on calcium homeostasis and hydrogen peroxide and superoxide anions in rat myocardial mitochondria.
1. Taurine and homocysteine are metabolites of methionine. Hyperhomocysteinaemia is one of the risk factors for cardiovascular disease. Although taurine may be a cardiovascular cytoprotective substance, we hypothesized that it may antagonize the effects of homocysteine on myocardial mitochondrial function. 2. We studied the effects of taurine and homocysteine on [(45)Ca] uptake, Ca(2+)-ATPase activity and generation of hydrogen peroxide and superoxide anions in vitro in rat isolated myocardial mitochondria. 3. Results showed that the inhibition of mitochondrial [(45)Ca] uptake by homocysteine (0.1, 0.5 and 1.0 mmol/L) was concentration dependent. Taurine (5, 10 and 20 mmol/L) promoted [(45)Ca] uptake in a concentration-dependent manner, as well as concentration dependently reducing the homocysteine (0.5 mmol/L)-induced inhibition of mitochondrial [(45)Ca] uptake. 4. Homocysteine significantly inhibited mitochondrial Ca(2+)-ATPase activity, whereas taurine had a diphasic action on this activity. Taurine, at 5 and 10 mmol/L, increased Ca(2+)-ATPase activity (P < 0.01), but 20 mmol/L taurine inhibited Ca(2+)-ATPase activity (P < 0.05). Taurine attenuated the inhibitory effect of homocysteine on Ca(2+)-ATPase activity. 5. Homocysteine stimulated the generation of hydrogen peroxide and superoxide anions. Taurine had no effect on the generation of the anions, but inhibited their homocysteine-stimulated generation. 6. These results indicate that taurine and homocysteine have opposite effects in myocardial mitochondria with regard to [(45)Ca] uptake, Ca(2+)-ATPase activity and the generation of hydrogen peroxide and superoxide anions. Our results may show an important mechanism for the cardiovascular protective effects of taurine.
Chang
Lin
L
Institute of Cardiovascular Disease Research, The First Hospital, Beijing, People's Republic of China. changlin73@163.com
Zhao
Jing
J
Xu
Jianxin
J
Jiang
Wei
W
Tang
Chao Shu
CS
Qi
Yong Fen
YF
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006706:Homeostasis / Q000187:drug effects* / Q000502:physiology; D006710:Homocysteine / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism; D013654:Taurine / Q000494:pharmacology*
D006710:Homocysteine; D013481:Superoxides; D013654:Taurine; D006861:Hydrogen Peroxide; D002118:Calcium