Abstract:
:Micromolar concentrations of lipoic acid racemate added to a working rat heart during hypoxia have been previously found to improve aortic flow during subsequent reoxygenation. Since the R-form represents the naturally occurring form of lipoic acid, and the S-form does not reveal a positive influence on ATP synthesis in isolated mitoplasts, a dose/response curve of both enantiomers has been performed in working rat hearts. After the end of perfusion mitochondria were isolated and further analysed. At a concentration of 0.05-0.1 mumol of the R-enantiomer, aortic flow rises precipitously during reoxygenation, reaching over 70% of normoxic values compared to 50% of the controls. By contrast, with the S-enantiomer a value of about 60% is attained at 1 mumol, only. Accordingly, ATPase activity in mitochondria isolated from rat hearts previously treated with 0.05-0.1 mumol of the R- or S-enantiomer was significantly decreased or increased respectively. Consequently, whereas mitochondrial ATP synthesis was increased when the R-enantiomer was previously added to the working heart at 0.05-0.1 mumol concentration, with the S-enantiomer ATP synthesis remained within the control range. Mitochondrial membrane fluidity, measured with diphenylhexatriene, revealed a trend towards increase with the R- and decrease with the S-enantiomer. The total amount of thiol added at 0.1 mumol concentration is consistent with a value of 2 nmol/mg mitochondrial protein. This value has previously been found to be connected with -SH groups which add oligomycin-sensitivity to the ATPase complex. It is suggested that oligomycin-sensitive mitochondrial -SH groups contribute to the overall efficiency of low concentrations of lipoic acid R-enantiomer to enhance aortic flow.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Zimmer G,Beikler TK,Schneider M,Ibel J,Tritschler H,Ulrich Hdoi
10.1016/0022-2828(95)90012-8subject
Has Abstractpub_date
1995-09-01 00:00:00pages
1895-903issue
9eissn
0022-2828issn
1095-8584journal_volume
27pub_type
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更新日期:1995-09-01 00:00:00
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