Mitochondria superoxide dismutase mimetic inhibits peroxide-induced oxidative damage and apoptosis: Role of mitochondrial superoxide

Dhanasekaran, Anuradha; Kotamraju, Srigiridhar; Karunakaran, C.; Kalivendi, Shasi V.; Thomas, Simmy; Joseph, Joy; Kalyanaraman, Balaraman

doi:10.1016/j.freeradbiomed.2005.04.016

Cited by 186 publications

(169 citation statements)

References 76 publications

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“…These compounds possess a positively charged moiety (triphenylphosphonium cation) that drives them into mitochondria and a lipophilic alkyl chain that facilitates their transfer across the lipid bilayer. At the end of the alkyl chain, different redoxactive compounds have been attached, including nitroxides (18,90,227,228,305,308). Mitochondrially targeted oligopeptides have been attached to Mn porphyrins as well (18).…”

Section: B Antioxidantsmentioning

confidence: 99%

“…Dhanasekaran et al (318,319), by using Michael Murphy strategy to target mitochondria, showed that mito-carboxy proxyl, but not untagged nitroxide, effectively inhibited mitochondrial oxidative damage (90). The activity is presumably due to the nitroxide being reduced by ubiquinol within respiring mitochondria (90,318,319).…”

Section: The Protective Effects Of Nitroxides In Vitro and In Vivomentioning

confidence: 99%

“…The activity is presumably due to the nitroxide being reduced by ubiquinol within respiring mitochondria (90,318,319). Jiang et al (163) proposed peptidyl nitroxide conjugates for targeting mitochondria.…”

Section: The Protective Effects Of Nitroxides In Vitro and In Vivomentioning

confidence: 99%

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Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

470

689

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Oxidative stress has become widely viewed as an underlying condition in a number of diseases, such as ischemia-reperfusion disorders, central nervous system disorders, cardiovascular conditions, cancer, and diabetes. Thus, natural and synthetic antioxidants have been actively sought. Superoxide dismutase is a first line of defense against oxidative stress under physiological and pathological conditions. Therefore, the development of therapeutics aimed at mimicking superoxide dismutase was a natural maneuver. Metalloporphyrins, as well as Mn cyclic polyamines, Mn salen derivatives and nitroxides were all originally developed as SOD mimics. The same thermodynamic and electrostatic properties that make them potent SOD mimics may allow them to reduce other reactive species such as peroxynitrite, peroxynitrite-derived CO 3 _ À , peroxyl radical, and less efficiently H 2 O 2 . By doing so SOD mimics can decrease both primary and secondary oxidative events, the latter arising from the inhibition of cellular transcriptional activity. To better judge the therapeutic potential and the advantage of one over the other type of compound, comparative studies of different classes of drugs in the same cellular and=or animal models are needed. We here provide a comprehensive overview of the chemical properties and some in vivo effects observed with various classes of compounds with a special emphasis on porphyrin-based compounds. Antioxid. Redox Signal. 13, 877-918.

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Section: B Antioxidantsmentioning

confidence: 99%

Section: The Protective Effects Of Nitroxides In Vitro and In Vivomentioning

confidence: 99%

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Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Batinić‐Haberle

Rebouças

Spasojević

2010

Antioxidants & Redox Signaling

470

689

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“…Proxyl nitroxides derivatized at the 3-position with alkylphosphonium groups were shown to retain their radical scavenging and SOD mimetic activity and localize effectively to mitochondria even when administered at concentrations ~3 orders of magnitude lower than those used with unsubstituted nitroxides. This suggests that a novel approach of using low total doses of certain nitroxides may achieve high local concentrations and provide protection against oxidative stress [26]. More recently, targeted nitrones, which are precursors of nitroxides, were synthesized [27].…”

Section: Nitroxides and Cell Signalingmentioning

confidence: 99%

The chemistry and biology of nitroxide compounds

Soule

Hyodo

Matsumoto

et al. 2007

Free Radical Biology and Medicine

467

387

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Cyclic nitroxides are a diverse range of stable free radicals that have unique antioxidant properties. Because of their ability to interact with free radicals, they have been used for many years as biophysical tools. During the past 15-20 years, however, many interesting biochemical interactions have been discovered and harnessed for therapeutic applications. Biologically relevant effects of nitroxides have been described including their ability to degrade superoxide and peroxide, inhibit Fenton reactions and undergo radical-radical recombination. Cellular studies defined the activity of nitroxides in vitro. By modifying oxidative stress and altering the redox status of tissues, nitroxides have been found to interact with and alter many metabolic processes. These interactions can be exploited for therapeutic and research use including protection against ionizing radiation, as probes in functional magnetic resonance imaging, cancer prevention and treatment, control of hypertension and weight, and protection from damage resulting from ischemia/reperfusion injury. While much remains to be done, many applications have been well studied and some are presently being tested in clinical trials. The therapeutic and research uses of nitroxide compounds are reviewed here with a focus on the progress from initial development to modern trials.

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“…One such compound is triphenylphosphonium cation (TPP), which has been used for measuring the mitochondrial inner membrane potential. Estimates suggest that linking antioxidants to TPP increases their accumulation in the mitochondrial matrix by several hundred-fold [79][80][81]. Examples of such mitochondria-targeted antioxidants include MitoVitE (TPP coupled to alpha-tocopherol), Mito-Q (TPP coupled to ubiquinone), Mito-PBN (TPP coupled to PBN), and Mito-CP (TPP coupled to carboxy-proxyl nitroxide).…”

Section: Figmentioning

confidence: 99%

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

et al. 2011

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Summary: Traumatic injury to the mammalian spinal cord is a highly dynamic process characterized by a complex pattern of pervasive and destructive biochemical and pathophysiological events that limit the potential for functional recovery. Currently, there are no effective therapies for the treatment of spinal cord injury (SCI) and this is due, in part, to the widespread impact of the secondary injury cascades, including edema, ischemia, excitotoxicity, inflammation, oxidative damage, and activation of necrotic and apoptotic cell death signaling events. In addition, many of the signaling pathways associated with these cascades intersect and initiate other secondary injury events. Therefore, it can be argued that therapeutic strategies targeting a specific biochemical cascade may not provide the best approach for promoting functional recovery. A "systems approach" at the subcellular level may provide a better strategy for promoting cell survival and function and, as a consequence, improve functional outcomes following SCI. One such approach is to study the impact of SCI on the biology and function of mitochondria, which serve a major role in cellular bioenergetics, function, and survival. In this review, we will briefly describe the importance and unique properties of mitochondria in the spinal cord, and what is known about the response of mitochondria to SCI. We will also discuss a number of strategies with the potential to promote mitochondrial function following SCI.

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Mitochondria superoxide dismutase mimetic inhibits peroxide-induced oxidative damage and apoptosis: Role of mitochondrial superoxide

Cited by 186 publications

References 76 publications

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

Superoxide Dismutase Mimics: Chemistry, Pharmacology, and Therapeutic Potential

The chemistry and biology of nitroxide compounds

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

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