NDLI: Mild uncoupling of respiration and phosphorylation as a mechanism providing nephro- and neuroprotective effects of penetrating cations of the SkQ family

Content Provider	Springer Nature Link
Author	Plotnikov, E. Y. Silachev, D. N. Jankauskas, S. S. Rokitskaya, T. I. Chupyrkina, A. A. Pevzner, I. B. Zorova, L. D. Isaev, N. K. Antonenko, Y. N. Skulachev, V. P. Zorov, D. B.
Copyright Year	2012
Abstract	It is generally accepted that mitochondrial production of reactive oxygen species is nonlinearly related to the value of the mitochondrial membrane potential with significant increment at values exceeding 150 mV. Due to this, high values of the membrane potential are highly dangerous, specifically under pathological conditions associated with oxidative stress. Mild uncoupling of oxidative phosphorylation is an approach to preventing hyperpolarization of the mitochondrial membrane. We confirmed data obtained earlier in our group that dodecylrhodamine 19 (C12R1) (a penetrating cation from SkQ family not possessing a plastoquinone group) has uncoupling properties, this fact making it highly potent for use in prevention of pathologies associated with oxidative stress induced by mitochondrial hyperpolarization. Further experiments showed that C12R1 provided nephroprotection under ischemia/reperfusion of the kidney as well as under rhabdomyolysis through diminishing of renal dysfunction manifested by elevated level of blood creatinine and urea. Similar nephroprotective properties were observed for low doses (275 nmol/kg) of the conventional uncoupler 2,4-dinitrophenol. Another penetrating cation that did not demonstrate protonophorous activity (SkQR4) had no effect on renal dysfunction. In experiments with induced ischemic stroke, C12R1 did not have any effect on the area of ischemic damage, but it significantly lowered neurological deficit. We conclude that beneficial effects of penetrating cation derivatives of rhodamine 19 in renal pathologies and brain ischemia may be at least partially explained by uncoupling of oxidation and phosphorylation.
Starting Page	1029
Ending Page	1037
Page Count	9
File Format	PDF
ISSN	00062979
Journal	Biochemistry (Moscow)
Volume Number	77
Issue Number	9
e-ISSN	16083040
Language	English
Publisher	SP MAIK Nauka/Interperiodica
Publisher Date	2012-09-15
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	ischemia rhabdomyolysis kidney brain stroke oxidative stress mitochondria-targeted compounds SkQ mitochondria Microbiology Biochemistry Biomedicine general Bioorganic Chemistry
Content Type	Text
Resource Type	Article
Subject	Biochemistry Biophysics Geriatrics and Gerontology

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