Glycyrrhetinic acid as inhibitor or amplifier of permeability transition in rat heart mitochondria

被引:21
作者
Battaglia, Valentina [1 ]
Brunati, Anna Maria [1 ]
Fiore, Cristina [2 ]
Rossi, Carlo Alberto [1 ]
Salvi, Mauro [1 ]
Tibaldi, Elena [1 ]
Palermo, Mario [3 ]
Armanini, Decio [2 ]
Toninello, Antonio [1 ]
机构
[1] Univ Padua, Dept Biol Chem, CNR, Inst Neurosci, I-35121 Padua, Italy
[2] Univ Padua, Dept Med & Surg Sci Endocrinol, I-35121 Padua, Italy
[3] Univ Sassari, Serv Endocrinol, I-07100 Sassari, Italy
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2008年 / 1778卷 / 01期
关键词
glycyrrhetinic acid; mitochondria; permeability transition; heart;
D O I
10.1016/j.bbamem.2007.10.008
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Glycyrrhetinic acid (GE), a hydrolysis product of glycyrrhizic acid, one of the main constituents of licorice root, is able, depending on its concentration, to prevent or to induce the mitochondrial permeability transition (NIPT) (a phenomenon related to oxidative stress) in rat heart mitochondria (RHM). In RHM, below a threshold concentration of 7.5 mu M, GE prevents oxidative stress and NIPT induced by supraphysiological Ca2+ concentrations. Above this concentration, GE induces oxidative stress by interacting with a Fe-S centre of Complex 1, thus producing ROS, and amplifies the opening of the transition pore, once again induced by Ca2+. GE also inhibits Ca2+ transport in RHM, thereby preventing the oxidative stress induced by the cation. However, the reduced amount of Ca2+ transported in the matrix is sufficient to predispose adenine nucleotide translocase for pore opening. Comparisons between observed results and the effects of GE in rat liver mitochondria (RLM), in which the drug induces only NIPT without exhibiting any protective effect, confirm that it interacts in a different way with RHM, suggesting tissue specificity for its action. The concentration dependence of the opposite effects of GE, in RHM but not RLM, is most probably due to the existence of a different, more complex, pathway by means of which GE reaches its target. It follows that high GE concentrations are necessary to stimulate the oxidative stress capable of inducing MPT, because of the above effect, which prevents the interaction of low concentrations of GE with the Fe-S centre. The reported results also explain the mechanism of apoptosis induction by GE in cardiomyocytes. (c) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:313 / 323
页数:11
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