The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/–/ApoE–/– mice

Mercer, John R.; Yu, Emma; Figg, Nichola; Cheng, Kian Kai; Prime, Tracy A.; Griffin, Julian L.; Masoodi, Mojgan; Vidal-Puig, António; Murphy, Michael P.; Bennett, Martin R.

doi:10.1016/j.freeradbiomed.2011.11.026

Cited by 153 publications

(121 citation statements)

References 19 publications

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“…To date, the utilities of a therapeutic strategy using MitoQ have been demonstrated in in vivo experiments using various disease model animals [15,[34][35][36]. Moreover, MitoQ has been investigated in clinical trials [20,37,38] and is expected to be promising candidate for a mitochondrial medicine.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Yamada

Nakamura

Abe

et al. 2015

Journal of Controlled Release

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We herein report on a mitochondrial therapeutic effect based on the delivery of coenzyme Q10 (CoQ10), an anti-oxidant, to in vivo mitochondria using a MITO-Porter, a liposome-based mitochondrial delivery system that functions via membrane fusion. To evaluate the effects, we used a mouse liver ischemia/reperfusion injury (I/R injury) model, in which mitochondrial reactive oxygen species are overexpressed. We packaged CoQ10 in the lipid phase of a MITO-Porter and optimized the mitochondrial fusogenic activities to produce the CoQ10-MITO-Porter. A histological observation of the carriers in the liver by confocal laser scanning microscopy was done and the accumulation of the carrier labeled with a radio isotope in the liver confirmed that the CoQ10-MITO-Porter was delivered to liver mitochondria via systemic injection. These analytical results permitted us to optimize the compositions of the CoQ10-MITO-Porter so as to permit it to efficiently accumulate in mouse liver mitochondria.Finally, we applied the optimized CoQ10-MITO-Porter to mice via tail vein injection, and hepatic I/R injury was then induced, followed by measuring serum alanine aminotransferase (ALT) levels, a marker of liver injury. We confirmed that the use of the CoQ10-MITO-Porter resulted in a significant decrease in serum ALT levels, indicating that in vivo mitochondrial delivery of the CoQ10 via MITO-Porter prevents I/R injury in mice livers. This provides a demonstration of the potential use of such a delivery system in mitochondrial therapies.

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Section: Discussionmentioning

confidence: 99%

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Yamada

Nakamura

Abe

et al. 2015

Journal of Controlled Release

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“…In subsequent experiments, we found that the TT genotype was associated with less severe coronary stenosis, indicating that the TT genotype was a protective factor for coronary heart disease (Li et al, 2011). In addition, ATM heterozygosity in ApoE null mice promotes atherosclerosis and multiple features of metabolic syndrome, including hypertension, hypercholesterolemia, hepatic steatosis, glucose intolerance, and alterations in lipid metabolism (Mercer et al, 2012). Coronary and aortic atherosclerosis and its associated diseases have also been observed in ATM-deficient mice (Herbig et al, 2006), suggesting that a decreased expression level of the ATM gene is a risk factor for vascular diseases.…”

Section: Discussionmentioning

confidence: 90%

Association between the rs189037 single nucleotide polymorphism in the ATM gene promoter and cognitive impairment

et al. 2015

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ABSTRACT. The aim of this study was to explore the existence of a relationship between the rs189037 single nucleotide polymorphism (SNP) of the ataxia telangiectasia mutated (ATM) gene and cognitive impairment in the elderly (aged 60 years and above). In a cohort, 505 residents of Suinung City were consecutively recruited and their cognitive function was measured using a 30-point Mini-Mental State Examination (MMSE). The subjects were divided into cognitive impairment group and control group on the basis of MMSE scores. Presence of the rs189037 SNP variant was examined using polymerase chain reaction-restriction fragment length polymorphism. The prevalence rates of cognitive impairment were 32.7% in the whole 4585 ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 4584-4592 (2015) Association between ATM and cognitive impairment sample. The genotype frequencies of the rs189037 polymorphism were 33.5% (CC), 50.7% (CT), and 15.8% (TT); the C and T allele frequencies were 58.8 and 41.2%, respectively. No significant differences in the frequency distributions of the CC, CT and TT genotypes were observed between cognitively impaired and control groups. We found that the rs189037 SNP was not directly correlated with cognitive impairment among the elderly Chinese Han population.

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“…Several other studies have used MitoQ10 in a variety of animal models of disease [102] and the results indicate that MitoQ10 protects against liver damage in an animal model of sepsis [103], contributes to the aetiology of the metabolic syndrome and atherosclerosis in a mouse model [104] protects pancreatic β-cells against oxidative stress and improves insulin secretion in glucotoxicity and glucolipotoxicity [105] and even protects against oxidative stress and cell death in the brain of rats exposed to the insecticide dichlorvos [106]. Importantly, the first clinical evidence of a potential benefit of MitoQ10 in humans comes from a study that MitoQ10 reduces liver damage induced by hepatitis virus infection [107].…”

Section: Antioxidant Defensesmentioning

confidence: 99%

Protection Against Oxidative Stress and “IGF-I Deficiency Conditions”

Morón¹,

Castilla‐Cortázar²

2012

Antioxidant Enzyme

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The mitochondria-targeted antioxidant MitoQ decreases features of the metabolic syndrome in ATM+/–/ApoE–/– mice

Cited by 153 publications

References 19 publications

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Mitochondrial delivery of Coenzyme Q10 via systemic administration using a MITO-Porter prevents ischemia/reperfusion injury in the mouse liver

Association between the rs189037 single nucleotide polymorphism in the ATM gene promoter and cognitive impairment

Protection Against Oxidative Stress and “IGF-I Deficiency Conditions”

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