A short-chain alkyl derivative of Rhodamine 19 acts as a mild uncoupler of mitochondria and a neuroprotector

被引：38

作者：

Khailova, Ljudmila S. ^{[1
,2
]}

Silachev, Denis N. ^{[1
,2
]}

Rokitskaya, Tatyana I. ^{[1
,2
]}

Avetisyan, Armine V. ^{[1
,2
]}

Lyamsaev, Konstantin G. ^{[1
,2
]}

Severina, Irma I. ^{[1
,2
]}

Il'yasova, Tatyana M. ^{[1
,2
]}

Gulyaev, Mikhail V. ^{[4
]}

Dedukhova, Vera I. ^{[1
,2
]}

Trendeleva, Tatyana A. ^{[5
]}

Plotnikov, Egor Y. ^{[1
,2
]}

Zvyagilskaya, Renata A. ^{[2
,5
]}

Chernyak, Boris V. ^{[1
,2
]}

Zorov, Dmitry B. ^{[1
,2
]}

Antonenko, Yuri N. ^{[1
,2
]}

Skulachev, Vladimir P. ^{[1
,2
,3
]}

机构：

[1] Moscow MV Lomonosov State Univ, Belozersky Inst Phys Chem Biol, Moscow 119991, Russia

[2] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow 119991, Russia

[3] Moscow MV Lomonosov State Univ, Fac Bioengn & Bioinformat, Moscow 119991, Russia

[4] Moscow MV Lomonosov State Univ, Fac Fundamental Med, Moscow 117192, Russia

[5] Russian Acad Sci, AN Bach Inst Biochem, Moscow 119071, Russia

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS | 2014年 / 1837卷 / 10期

基金：

俄罗斯基础研究基金会; 俄罗斯科学基金会;

关键词：

Mitochondria; Mild uncoupler; Protonophore; Rhodamine; Membrane potential; TRAUMATIC BRAIN-INJURY; NEURONAL DEATH; OXIDATIVE-PHOSPHORYLATION; PENETRATING CATIONS; PROTEIN-2; PROTECTS; PROTON TRANSPORT; FATTY-ACIDS; MECHANISM; OXYGEN; ISCHEMIA;

D O I：

10.1016/j.bbabio.2014.07.006

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：

Limited uncoupling of oxidative phosphorylation is known to be-beneficial in various laboratory models of diseases. The search for cationic uncouplers is promising as their protonophorous effect is self-limiting because these uncouplers lower membrane potential which is the driving force for their accumulation in mitochondria. In this work, the penetrating cation Rhodamine 19 butyl ester (C(4)R1) was found to decrease membrane potential and to stimulate respiration of mitochondria, appearing to be a stronger uncoupler than its more hydrophobic analog Rhodamine 19 dodecyl ester (C(12)R1). Surprisingly, C(12)R1 increased H+ conductance of artificial bilayer lipid membranes or induced mitochondria swelling in potassium acetate with valinomycin at concentrations lower than C(4)R1. This paradox might be explained by involvement of mitochondrial proteins in the uncoupling action of C(4)R1. In experiments with HeLa cells, C(4)R1 rapidly and selectively accumulated in mitochondria and stimulated oligomycin-sensitive respiration as a mild uncoupler. C(4)R1 was effective in preventing oxidative stress induced by brain ischemia and reperfusion in rats: it suppressed stroke-induced brain swelling and prevented the decline in neurological status more effectively than C(12)R1. Thus, C(4)R1 seems to be a promising example of a mild uncoupler efficient in treatment of brain pathologies related to oxidative stress. (C) 2014 Elsevier B.V. All rights reserved.

引用

页码：1739 / 1747

页数：9

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