• Je něco špatně v tomto záznamu ?

A mitochondria-targeted derivative of ascorbate: MitoC

PG. Finichiu, DS. Larsen, C. Evans, L. Larsen, TP. Bright, EL. Robb, J. Trnka, TA. Prime, AM. James, RA. Smith, MP. Murphy,

. 2015 ; 89 (-) : 668-78. [pub] 20151008

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc17000967

Mitochondrial oxidative damage contributes to a wide range of pathologies. One therapeutic strategy to treat these disorders is targeting antioxidants to mitochondria by conjugation to the lipophilic triphenylphosphonium (TPP) cation. To date only hydrophobic antioxidants have been targeted to mitochondria; however, extending this approach to hydrophilic antioxidants offers new therapeutic and research opportunities. Here we report the development and characterization of MitoC, a mitochondria-targeted version of the hydrophilic antioxidant ascorbate. We show that MitoC can be taken up by mitochondria, despite the polarity and acidity of ascorbate, by using a sufficiently hydrophobic link to the TPP moiety. MitoC reacts with a range of reactive species, and within mitochondria is rapidly recycled back to the active ascorbate moiety by the glutathione and thioredoxin systems. Because of this accumulation and recycling MitoC is an effective antioxidant against mitochondrial lipid peroxidation and also decreases aconitase inactivation by superoxide. These findings show that the incorporation of TPP function can be used to target polar and acidic compounds to mitochondria, opening up the delivery of a wide range of bioactive compounds. Furthermore, MitoC has therapeutic potential as a new mitochondria-targeted antioxidant, and is a useful tool to explore the role(s) of ascorbate within mitochondria.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc17000967
003      
CZ-PrNML
005      
20170117093011.0
007      
ta
008      
170103s2015 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.freeradbiomed.2015.07.160 $2 doi
024    7_
$a 10.1016/j.freeradbiomed.2015.07.160 $2 doi
035    __
$a (PubMed)26453920
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Finichiu, Peter G $u MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge CB2 0XY, UK.
245    12
$a A mitochondria-targeted derivative of ascorbate: MitoC / $c PG. Finichiu, DS. Larsen, C. Evans, L. Larsen, TP. Bright, EL. Robb, J. Trnka, TA. Prime, AM. James, RA. Smith, MP. Murphy,
520    9_
$a Mitochondrial oxidative damage contributes to a wide range of pathologies. One therapeutic strategy to treat these disorders is targeting antioxidants to mitochondria by conjugation to the lipophilic triphenylphosphonium (TPP) cation. To date only hydrophobic antioxidants have been targeted to mitochondria; however, extending this approach to hydrophilic antioxidants offers new therapeutic and research opportunities. Here we report the development and characterization of MitoC, a mitochondria-targeted version of the hydrophilic antioxidant ascorbate. We show that MitoC can be taken up by mitochondria, despite the polarity and acidity of ascorbate, by using a sufficiently hydrophobic link to the TPP moiety. MitoC reacts with a range of reactive species, and within mitochondria is rapidly recycled back to the active ascorbate moiety by the glutathione and thioredoxin systems. Because of this accumulation and recycling MitoC is an effective antioxidant against mitochondrial lipid peroxidation and also decreases aconitase inactivation by superoxide. These findings show that the incorporation of TPP function can be used to target polar and acidic compounds to mitochondria, opening up the delivery of a wide range of bioactive compounds. Furthermore, MitoC has therapeutic potential as a new mitochondria-targeted antioxidant, and is a useful tool to explore the role(s) of ascorbate within mitochondria.
650    _2
$a zvířata $7 D000818
650    _2
$a antioxidancia $x chemie $x farmakologie $7 D000975
650    _2
$a kyselina askorbová $x chemie $x farmakologie $7 D001205
650    _2
$a vysokoúčinná kapalinová chromatografie $7 D002851
650    _2
$a lékové transportní systémy $x metody $7 D016503
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a jaterní mitochondrie $x účinky léků $x metabolismus $7 D008930
650    _2
$a oxidace-redukce $7 D010084
650    _2
$a oxidační stres $x účinky léků $7 D018384
650    _2
$a krysa rodu Rattus $7 D051381
650    _2
$a potkani Wistar $7 D017208
655    _2
$a časopisecké články $7 D016428
700    1_
$a Larsen, David S $u Department of Chemistry, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.
700    1_
$a Evans, Cameron $u Department of Chemistry, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.
700    1_
$a Larsen, Lesley $u Department of Chemistry, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.
700    1_
$a Bright, Thomas P $u MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge CB2 0XY, UK.
700    1_
$a Robb, Ellen L $u MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge CB2 0XY, UK.
700    1_
$a Trnka, Jan $u Laboratory for Metabolism and Bioenergetics, Third Faculty of Medicine, Charles University, 100 00 Prague 10, Czech Republic.
700    1_
$a Prime, Tracy A $u MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge CB2 0XY, UK.
700    1_
$a James, Andrew M $u MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge CB2 0XY, UK.
700    1_
$a Smith, Robin A J $u Department of Chemistry, University of Otago, P.O. Box 56, Dunedin 9054, New Zealand.
700    1_
$a Murphy, Michael P $u MRC Mitochondrial Biology Unit, Wellcome Trust/MRC Building, Cambridge CB2 0XY, UK. Electronic address: mpm@mrc-mbu.cam.ac.uk.
773    0_
$w MED00001857 $t Free radical biology & medicine $x 1873-4596 $g Roč. 89, č. - (2015), s. 668-78
856    41
$u https://pubmed.ncbi.nlm.nih.gov/26453920 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20170103 $b ABA008
991    __
$a 20170117093117 $b ABA008
999    __
$a ok $b bmc $g 1180107 $s 961534
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2015 $b 89 $c - $d 668-78 $e 20151008 $i 1873-4596 $m Free radical biology & medicine $n Free Radic Biol Med $x MED00001857
LZP    __
$a Pubmed-20170103

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace