Kagan, VE and Wipf, P and Stoyanovsky, D and Greenberger, JS and Borisenko, G and Belikova, NA and Yanamala, N and Samhan Arias, AK and Tungekar, MA and Jiang, J and Tyurina, YY and Ji, J and Klein-Seetharaman, J and Pitt, BR and Shvedova, AA and Bayir, H
(2009)
Mitochondrial targeting of electron scavenging antioxidants: Regulation of selective oxidation vs random chain reactions.
Advanced Drug Delivery Reviews, 61 (14).
1375 - 1385.
ISSN 0169-409X
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Abstract
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. © 2009 Elsevier B.V. All rights reserved.
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Details
Item Type: |
Article
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Status: |
Published |
Creators/Authors: |
Creators | Email | Pitt Username | ORCID ![](/images/orcid_id_24x24.png) |
---|
Kagan, VE | kagan@pitt.edu | KAGAN | | Wipf, P | pwipf@pitt.edu | PWIPF | | Stoyanovsky, D | das11@pitt.edu | DAS11 | 0000-0001-5591-4780 | Greenberger, JS | joelg@pitt.edu | JOELG | | Borisenko, G | | | | Belikova, NA | | | | Yanamala, N | | | | Samhan Arias, AK | | | | Tungekar, MA | | | | Jiang, J | jjf73@pitt.edu | JJF73 | | Tyurina, YY | | | | Ji, J | | | | Klein-Seetharaman, J | | | | Pitt, BR | brucep@pitt.edu | BRUCEP | | Shvedova, AA | | | | Bayir, H | | | |
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Date: |
30 November 2009 |
Date Type: |
Publication |
Journal or Publication Title: |
Advanced Drug Delivery Reviews |
Volume: |
61 |
Number: |
14 |
Page Range: |
1375 - 1385 |
DOI or Unique Handle: |
10.1016/j.addr.2009.06.008 |
Schools and Programs: |
Dietrich School of Arts and Sciences > Chemistry |
Refereed: |
Yes |
ISSN: |
0169-409X |
Article Type: |
Review |
MeSH Headings: |
Animals; Antioxidants--pharmacology; Apoptosis--drug effects; Drug Delivery Systems--methods; Electron Transport Complex I--metabolism; Free Radical Scavengers--chemistry; Free Radical Scavengers--pharmacokinetics; Humans; Mitochondria--drug effects; Mitochondria--metabolism; Models, Biological; Molecular Structure; Oxidation-Reduction--drug effects; Oxidative Stress--drug effects; Reactive Oxygen Species--metabolism |
Other ID: |
NLM NIHMS142023, NLM PMC2784017 |
PubMed Central ID: |
PMC2784017 |
PubMed ID: |
19716396 |
Date Deposited: |
07 Jun 2013 20:42 |
Last Modified: |
10 Mar 2021 06:25 |
URI: |
http://d-scholarship-dev.library.pitt.edu/id/eprint/18829 |
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