TY  - JOUR
AU  - Kagan, V.E.
AU  - Wipf, P.
AU  - Stoyanovsky, D.
AU  - Greenberger, J.S.
AU  - Borisenko, G.
AU  - Belikova, N.A.
AU  - Yanamala, N.
AU  - Samhan Arias, A.K.
AU  - Tungekar, M.A.
AU  - Jiang, J.
AU  - Tyurina, Y.Y.
AU  - Ji, J.
AU  - Klein-Seetharaman, J.
AU  - Pitt, B.R.
AU  - Shvedova, A.A.
AU  - Bayir, H.
TI  - Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain  reactions
JO  - Advanced drug delivery reviews
VL  - 61
SN  - 0169-409X
CY  - Amsterdam [u.a.]
PB  - Elsevier Science
M1  - PreJuSER-8402
SP  - 1375 - 1385
PY  - 2009
N1  - This work was supported by NIH Grants U19 AIO68021, HL70755, HD057587, NS061817, NORA 927Z1LU, PittGrid (http://www.pittgrid. pitt.edu) and la junta de Extremadura -Consejeria de Infraestructuras y Desarrollo Tecnologico- y el Fondo Social Europeo (Orden 2008050288).
AB  - Effective regulation of highly compartmentalized production of reactive oxygen species and peroxidation reactions in mitochondria requires targeting of small molecule antioxidants and antioxidant enzymes into the organelles. This review describes recently developed approaches to mitochondrial targeting of small biologically active molecules based on: (i) preferential accumulation in mitochondria because of their hydrophobicity and positive charge (hydrophobic cations), (ii) binding with high affinity to an intra-mitochondrial constituent, and (iii) metabolic conversions by specific mitochondrial enzymes to reveal an active entity. In addition, targeted delivery of antioxidant enzymes via expression of leader sequences directing the proteins into mitochondria is considered. Examples of successful antioxidant and anti-apoptotic protection based on the ability of targeted cargoes to inhibit cytochrome c-catalyzed peroxidation of a mitochondria-specific phospholipid cardiolipin, in vitro and in vivo are presented. Particular emphasis is placed on the employment of triphenylphosphonium- and hemi-gramicidin S-moieties as two effective vehicles for mitochondrial delivery of antioxidants.
KW  - Animals
KW  - Antioxidants: pharmacology
KW  - Apoptosis: drug effects
KW  - Drug Delivery Systems: methods
KW  - Electron Transport Complex I: metabolism
KW  - Free Radical Scavengers: chemistry
KW  - Free Radical Scavengers: pharmacokinetics
KW  - Humans
KW  - Mitochondria: drug effects
KW  - Mitochondria: metabolism
KW  - Models, Biological
KW  - Molecular Structure
KW  - Oxidation-Reduction: drug effects
KW  - Oxidative Stress: drug effects
KW  - Reactive Oxygen Species: metabolism
KW  - Antioxidants (NLM Chemicals)
KW  - Free Radical Scavengers (NLM Chemicals)
KW  - Reactive Oxygen Species (NLM Chemicals)
KW  - Electron Transport Complex I (NLM Chemicals)
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:19716396
C2  - pmc:PMC2784017
UR  - <Go to ISI:>//WOS:000272600300014
DO  - DOI:10.1016/j.addr.2009.06.008
UR  - https://juser.fz-juelich.de/record/8402
ER  -