HMG1A and PPARG are differently expressed in the liver of fat and lean broilers

The expression of nine functional candidates for QT abdominal fat weight and relative abdominal fat content was investigated by real-time polymerase chain reaction (PCR) in the liver, adipose tissue, colon, muscle, pituitary gland and brain of broilers. The high mobility group AT-hook 1 (HMG1A) gene was up-regulated in liver with a ratio of means of 2.90 (P ≤ 0.01) in the «fatty» group (relative abdominal fat content 3.5 ± 0.18%, abdominal fat weight 35.4 ± 6.09 g) relative to the «lean» group (relative abdominal fat content 1.9 ± 0.56%, abdominal fat weight 19.2 ± 5.06 g). Expression of this gene was highly correlated with the relative abdominal fat content (0.70, P ≤ 0.01) and abdominal fat weight (0.70, P ≤ 0.01). The peroxisome proliferator-activated receptor gamma (PPARG) gene was also up-regulated in the liver with a ratio of means of 3.34 (P ≤ 0.01) in the «fatty» group relative to the «lean» group. Correlation of its expression was significant with both the relative abdominal fat content (0.55, P ≤ 0.05) and the abdominal fat weight (0.57, P ≤ 0.01). These data suggest that the HMG1A and PPARG genes were candidate genes for abdominal fat deposition in chickens. Searching of rSNPs in regulatory regions of the HMG1A and PPARG genes could provide a tool for gene-assisted selection

Association of PGC-1alpha polymorphisms with age of onset and risk of Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Peroxisome proliferator-activated receptor-γ co-activator (PGC)-1α is a transcriptional co-activator of antioxidant genes and a master regulator of mitochondrial biogenesis. Parkinson's disease (PD) is associated with oxidative stress and mitochondrial dysfunction and recent work suggests a role for PGC-1α. We hypothesized that the rs8192678 <it>PGC-1α </it>single nucleotide polymorphism (SNP) may influence risk or age of onset of PD. The A10398G mitochondrial SNP has been inversely associated with risk of PD in some studies. In the current study we analyzed whether rs8192678 or other <it>PGC-1α </it>SNPs affect PD risk or age of onset, singularly or in association with the A10398G SNP.</p> <p>Methods</p> <p>Genomic DNA samples from 378 PD patients and 173 age-matched controls were analyzed by multiplexed probe sequencing, followed by statistical analyses of the association of each SNP, alone or in combination, with risk or age of onset of PD. Adjustments were made for age of onset being less than the age of sampling, and for the observed dependence between these two ages. The PD samples were obtained as two separate cohorts, therefore statistical methods accounted for different sampling methods between the two cohorts, and data were analyzed using Cox regression adjusted for sampling in the risk set definition and in the model.</p> <p>Results</p> <p>The rs8192678 PGC-1α SNP was not associated with the risk of PD. However, an association of the <it>PGC-1α </it>rs8192678 GG variant with longevity was seen in control subjects (p = 0.019). Exploratory studies indicated that the CC variant of rs6821591 was associated with risk of early onset PD (p = 0.029), with PD age of onset (p = 0.047), and with longevity (p = 0.022). The rs2970848 GG allele was associated with risk of late onset PD (p = 0.027).</p> <p>Conclusions</p> <p>These data reveal possible associations of the <it>PGC-1α </it>SNPs rs6821591 and rs2970848 with risk or age of onset of PD, and of the <it>PGC-1α </it>rs8192678 GG and the rs6821591 CC variants with longevity. If replicated in other datasets, these findings may have important implications regarding the role of <it>PGC-1α </it>in PD and longevity.</p

1B/(−)IRE DMT1 Expression during Brain Ischemia Contributes to Cell Death Mediated by NF-κB/RelA Acetylation at Lys310

The molecular mechanisms responsible for increasing iron and neurodegeneration in brain ischemia are an interesting area of research which could open new therapeutic approaches. Previous evidence has shown that activation of nuclear factor kappa B (NF-κB) through RelA acetylation on Lys310 is the prerequisite for p50/RelA-mediated apoptosis in cellular and animal models of brain ischemia. We hypothesized that the increase of iron through a NF-κB-regulated 1B isoform of the divalent metal transporter-1 (1B/DMT1) might contribute to post-ischemic neuronal damage. Both in mice subjected to transient middle cerebral artery occlusion (MCAO) and in neuronally differentiated SK-N-SH cells exposed to oxygen-glucose-deprivation (OGD), 1A/DMT1 was only barely expressed while the 1B/DMT1 without iron-response-element (−IRE) protein and mRNA were early up-regulated. Either OGD or over-expression of 1B/(−)IRE DMT1 isoform significantly increased iron uptake, as detected by total reflection X-ray fluorescence, and iron-dependent cell death. Iron chelation by deferoxamine treatment or (−)IRE DMT1 RNA silencing displayed significant neuroprotection against OGD which concomitantly decreased intracellular iron levels. We found evidence that 1B/(−)IRE DMT1 was a target gene for RelA activation and acetylation on Lys310 residue during ischemia. Chromatin immunoprecipitation analysis of the 1B/DMT1 promoter showed there was increased interaction with RelA and acetylation of H3 histone during OGD exposure of cortical neurons. Over-expression of wild-type RelA increased 1B/DMT1 promoter-luciferase activity, the (−)IRE DMT1 protein, as well as neuronal death. Expression of the acetylation-resistant RelA-K310R construct, which carried a mutation from lysine 310 to arginine, but not the acetyl-mimic mutant RelA-K310Q, down-regulated the 1B/DMT1 promoter, consequently offering neuroprotection. Our data showed that 1B/(−)IRE DMT1 expression and intracellular iron influx are early downstream responses to NF-κB/RelA activation and acetylation during brain ischemia and contribute to the pathogenesis of stroke-induced neuronal damage

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion

In-vivo optical and PET detections of fibrillar tau lesions in a mouse model of tauopathies

Background: Intracellular inclusions of pathological tau fibrils are hallmark lesions in Alzheimer\u27s disease (AD) and associated tauopathies, and there has been a growing interest in the mechanistic links between fibrillar tau accumulation and neuronal deterioration. In-vivo visualization of tau lesions would thus serve the preclinical and clinical needs for pursuing the molecular etiology of neurodegenerative disorders and evaluating candidate disease-modifying therapies. This notion has led us to develop imaging agents capable of capturing tau aggregates in a living mouse model of tauopathies.Methods: An array of fluorescent chemicals were screened by assaying their in-vitro binding to recombinant tau fibrils and neuronal tau inclusions on brain sections from patients with diverse tauopathies and mice transgenic for the pathogenic P301S mutant tau. The selected compounds were intravenously injected into the tau transgenics, and ex-vivo labelings of tau lesions with these agents in excised brain samples were microscopically assessed. Pulse-laser optical and positron emission tomographic (PET) systems were then applied to in-vivo detections of tau pathologies in the transgenic mice with near-infrared fluorescent and 11C-labeled compounds, respectively. The PET data were also supplemented by in-vitro and ex-vivo autoradiographic analyses.Results: Chemical properties of the compounds such as structural dimensions and hydrophilicities were associated with their affinities for tau inclusions in a wide range of tauopathies as well as transgenics. A class of chemicals sharing the common core structure enabled ex-vivo visualization of aggregates in the transgenic mice. One of these putative imaging agents was suitable for the near-infrared optics, and was proven to bind to tau aggregated in living mouse brains based on the intensity and life-time of its fluorescent signals. Two other compounds of the same group were radiolabeled with 11C, and were demonstrated to allow both autoradiographic and PET detections of tau lesions in the transgenics.Conclusion: The present neuroimaging approaches using mouse models of the diseases provide insights into the structural basis of molecular interactions between tau fibrils and exogenous compounds, which would facilitate the development of diagnostic and therapeutic agents for AD and non-AD tauopathies.Alzheimer\u27s Association 2009 International Conference on Alzheimer\u27s Diseas