Targeting antioxidants to mitochondria: A new therapeutic direction

Sheu, Shey‐Shing; Nauduri, Dhananjaya; Anders, M.W.

doi:10.1016/j.bbadis.2005.10.007

Cited by 367 publications

(304 citation statements)

References 52 publications

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“…Most of these studies examined the genetic polymorphisms in essential genes, including Tolllike receptors, cytokines, and coagulation factors, and provided important insights into the mechanisms involved in the pathogenesis of sepsis-related organ dysfunction. 19 Mitochondria perform a variety of key cellular regulatory processes, such as ATP production, intracellular Ca 2ϩ regulation, reactive oxygen species (ROS) generation and detoxification, and apoptosis, 20 and mitochondrial dysfunction contributes significantly to the pathogenesis of sepsis and multiple organ dysfunction. 6,[21][22][23] Among mammalian organelles, the mitochondrion is unique, containing its own genome encoding 13 essential protein components of the mitochondrial respiratory chain.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in the Han population

Yang

Shou

Zhang

et al. 2008

Genetics in Medicine

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Purpose: To determine whether the main mitochondrial DNA (mtDNA) haplogroups of the Han people have an impact on long-term clinical outcome. Methods: We prospectively studied 181 individuals who were sequentially admitted to the intensive care unit. Demographic and clinical data were recorded along with clinical outcome over 180 days. Follow-up was completed for all study participants. We then determined the mtDNA haplogroups of the patients and 570 healthy, age-matched Han people from Zhejiang province, Southeast China, by analyzing sequences of hypervariable mtDNA segments and testing diagnostic polymorphisms in the mtDNA coding region with DNA probes. Result: The frequency of the main subhaplogroups of the Han population in the study cohort did not differ significantly from the control group. mtDNA haplogroup R, one of the three main mtDNA haplogroups of the Han people, was a strong independent predictor for the outcome of severe sepsis, conferring a 4.68-fold (95%

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in the Han population

Yang

Shou

Zhang

et al. 2008

Genetics in Medicine

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“…Based on its demonstrated lipid peroxyl scavenging activity, the improvement in functional recovery was associated with a decrease in the lipid peroxidation product malondialdehyde [63]. Although effective in some experimental models of SCI, the use of alpha-tocopherol alone has several disadvantages, including a lack of mitochondrial specificity and potential harmful side effects at high doses [64,65].…”

Section: Figmentioning

confidence: 99%

“…Other mitochondrial targeting antioxidants include aromatic cationic peptides, called SS tetrapeptides, which contain the phenolic antioxidant 2',6'-dimethyltyrosine linked to alternating aromatic and basic amino acid residues. At least four SS tetrapeptides (SS-02, SS-19, SS-20, and SS-31) have been generated that exhibit potent and mitochondria-specific antioxidant properties [64]. Similar to the TPP-linked antioxidants, these SS tetrapeptides accumulate in mitochondria in amounts that are several-fold higher than the extracellular concentrations.…”

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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“…14 Mitochondria have been considered an important target for cancer therapy, and quinones and hydroquinones are believed to function inside the mitochondria. [15][16][17] Therefore, there is no doubt that in order to reach their targets these molecules must cross several membranes, including mitochondrial membranes. On the other hand, it is well known that in-vivo antioxidant activity of polyphenols is limited by their ability to cross membranes.…”

Section: Introductionmentioning

confidence: 99%

Location, Orientation and Dynamics of Two Molecules With Mitochondrial Activity Dissolved in Anionic Lyomesophase: A ²h-NMR and Md Study

Bahamonde-Padilla¹,

Martínez-Cifuentes²,

Muñoz-Masson³

et al. 2012

J. Chil. Chem. Soc.

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ABSTRACT4,4-Dimethyl-5,8-dihydroanthracene-1,9,10(4H)-trione (Q1) and 9,10-Dihydroxy-4,4-dimethyl-5,8-dihydro-1(4H)-anthracenone (Q2), two molecules that inhibit cancer cell respiration, were selectively deuterated and dissolved in an anionic discotic nematic lyotropic liquid crystal (dnllc) solution. The solution provides a magnetic field oriented anisotropic medium, where the location, average orientation and dynamics of Q1 and Q2 were examined by measuring 2 H-NMR quadrupole splittings (Dn Q ) and 2 H longitudinal relaxation times (T 1 ). The NMR data shows that both molecules are strongly attached to the aggregate and, when dissolved, increase the alignment of the interface components with the magnetic field. However they present different average orientations. To assist with the interpretation of the experimental results, 300ns Molecular Dynamics (MD) trajectories of a bilayer model of the aggregate were calculated. The results show that both molecules spontaneously diffuse inside the bilayer, to locate in the limit between the hydrophobic core and the interface. The orientations of both molecules in the aggregate are determined by the formation of H-bonds with water.

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Targeting antioxidants to mitochondria: A new therapeutic direction

Cited by 367 publications

References 52 publications

Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in the Han population

Mitochondrial DNA haplogroup R predicts survival advantage in severe sepsis in the Han population

Targeting Mitochondrial Function for the Treatment of Acute Spinal Cord Injury

Location, Orientation and Dynamics of Two Molecules With Mitochondrial Activity Dissolved in Anionic Lyomesophase: A ²h-NMR and Md Study

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