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1.  A comparison among the tissue-specific effects of aging and calorie restriction on TFAM amount and TFAM-binding activity to mtDNA in rat 
Biochimica et biophysica acta  2014;1840(7):2184-2191.
Mitochondrial Transcription Factor A (TFAM) is regarded as a histone-like protein of mitochondrial DNA (mtDNA), performing multiple functions for this genome. Aging affects mitochondria in a tissue-specific manner and only calorie restriction (CR) is able to delay or prevent the onset of several age-related changes also in mitochondria.
Samples of the frontal cortex and soleus skeletal muscle from 6- and 26-month-old ad libitum-fed and 26-month-old calorie-restricted rats and of the livers from 18- and 28-month-old ad libitum-fed and 28-month-old calorie-restricted rats were used to detect TFAM amount, TFAM-binding to mtDNA and mtDNA content.
We found an age-related increase in TFAM amount in the frontal cortex, not affected by CR, versus an age-related decrease in the soleus and liver, fully prevented by CR. The semi-quantitative analysis of in vivo binding of TFAM to specific mtDNA regions, by mtDNA immunoprecipitation assay and following PCR, showed a marked age-dependent decrease in TFAM-binding activity in the frontal cortex, partially prevented by CR. An age-related increase in TFAM-binding to mtDNA, fully prevented by CR, was found in the soleus and liver. MtDNA content presented a common age-related decrease, completely prevented by CR in the soleus and liver, but not in the frontal cortex.
The modulation of TFAM expression, TFAM-binding to mtDNA and mtDNA content with aging and CR showed a trend shared by the skeletal muscle and liver, but not by the frontal cortex counterpart.
General significance: Aging and CR appear to induce similar mitochondrial molecular mechanisms in the skeletal muscle and liver, different from those elicited in the frontal cortex.
PMCID: PMC4335656  PMID: 24631828
Mitochondrial Transcription Factor A; Mitochondrial Transcription Factor; A–mitochondrial deoxyribonucleic acid binding; Tissue-specificity; Aging rat; Calorie restriction
2.  Fat-1 transgenic mice with elevated omega-3 fatty acids are protected from allergic airway responses 
Biochimica et biophysica acta  2011;1812(9):1164-1169.
Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been implicated in the alleviation of asthma. Recent studies have demonstrated that the n-3 PUFA derived lipid mediators, protectin D1 and resolvin E1, may act as potent resolution agonists in airway inflammation. The effects of the n-3 PUFA tissue status itself on asthma pathogenesis remains to be further investigated.
In this study allergic airway inflammation induced by allergen sensitization and aerosol challenge in Fat-1 and wild-type (WT) mice was investigated. Fat-1 transgenic mice displayed increased endogenous lung n-3 PUFA. When allergen-sensitized and aerosol-challenged, these animals had decreased airway inflammation with decreased leukocyte accumulation in bronchoalveolar lavage fluid (BALF) and lung parenchyma. The Fat-1 mice had a shift to the right in the dose-response relationship for methacholine induced bronchoconstriction with a significant increase in the log ED200. The Fat-1 mice had lower BALF concentrations of the pro-inflammatory cytokines IL-1α, IL-2, IL-5, IL-9, IL- 13, G-CSF, KC and RANTES. Furthermore, increased lung tissue amounts of the counter-regulatory mediators protectin D1 and resolvin E1 were found in Fat-1 mice after bronchoprovocative challenge.
These results therefore demonstrate a direct protective role for lung n-3 PUFA in allergic airway responses and an increased generation of protectin D1 and resolvin E1 in this context.
PMCID: PMC4325089  PMID: 21616147
Omega-3; resolvins; protectins; inflammation; asthma; Fat-1 mice
3.  Molecular and Bioenergetic Differences between Cells with African versus European Inherited Mitochondrial DNA Haplogroups: Implications for Population Susceptibility to Diseases 
Biochimica et biophysica acta  2013;1842(2):208-219.
The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP turnover rates and lower levels of ROS production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases.
PMCID: PMC4326177  PMID: 24200652
Mitochondrial haplogroups; transmitochondrial cybrids; inflammation; complement; mitochondria; complement activation; innate immunity; haplogroups; cybrids; retina
Biochimica et biophysica acta  2008;1781(4):192-199.
Intestinal FABP (IFABP) and liver FABP (LFABP), homologous proteins expressed at high levels in intestinal absorptive cells, employ markedly different mechanisms of fatty acid transfer to acceptor model membranes. Transfer from IFABP occurs during protein-membrane-collisional interactions, while for LFABP transfer occurs by diffusion through the aqueous phase. In addition, transfer from IFABP is markedly faster than from LFABP. The overall goal of this study was to further explore the structural differences between IFABP and LFABP which underlie their large functional differences in ligand transport. In particular, we addressed the role of the αI-helix domain in the unique transport properties of intestinal FABP. A chimeric protein was engineered with the ‘body’ (ligand binding domain) of IFABP and the αI-helix of LFABP (α(I)LβIFABP), and the fatty acid transfer properties of the chimeric FABP were examined using a fluorescence resonance energy transfer assay. The results showed a significant decrease in the absolute rate of FA transfer from α(I)LβIFABP compared to IFABP. The results indicate that the αI-helix is crucial for IFABP collisional FA transfer, and further indicate the participation of the αII-helix in the formation of a protein-membrane “collisional complex”. Photo-crosslinking experiments with a photoactivable reagent demonstrated the direct interaction of IFABP with membranes and further supports the importance of the αI helix of IFABP in its physical interaction with membranes.
PMCID: PMC4319566  PMID: 18284926
fatty acid binding protein; fatty acid; chimeric proteins; lipid metabolism; small intestine; lipid transport
5.  [No title available] 
PMCID: PMC3766385  PMID: 23567800
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PMCID: PMC3766491  PMID: 23648414
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PMCID: PMC3770773  PMID: 23660153
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PMCID: PMC3858408  PMID: 23668959
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PMCID: PMC3858447  PMID: 23872352
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PMCID: PMC3858512  PMID: 24021887
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PMCID: PMC3867519  PMID: 23899502
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PMCID: PMC3877165  PMID: 23680625
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PMCID: PMC3877175  PMID: 23886914
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PMCID: PMC3877202  PMID: 24071592
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PMCID: PMC3877210  PMID: 23891718
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PMCID: PMC3877419  PMID: 23732236
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PMCID: PMC3901642  PMID: 24275510
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PMCID: PMC3902145  PMID: 24269780
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PMCID: PMC3905326  PMID: 24252613
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PMCID: PMC3913072  PMID: 24296261
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PMCID: PMC3915056  PMID: 24269842
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PMCID: PMC3923981  PMID: 24286864
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PMCID: PMC3925188  PMID: 24291127
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PMCID: PMC3926667  PMID: 24275509
25.  [No title available] 
PMCID: PMC3928473  PMID: 24200678

Results 1-25 (2421)