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Markus Sällman Almén Emil K. Nilsson Josefin A. Jacobsson Ineta Kalnina Janis Klovins Robert Fredriksson Helgi B. Schiöth 《Gene》2014
The combination of the obesity epidemic and an aging population presents growing challenges for the healthcare system. Obesity and aging are major risk factors for a diverse number of diseases and it is of importance to understand their interaction and the underlying molecular mechanisms. Herein the authors examined the methylation levels of 27578 CpG sites in 46 samples from adult peripheral blood. The effect of obesity and aging was ascertained with general linear models. More than one hundred probes were correlated to aging, nine of which belonged to the KEGG group map04080. Additionally, 10 CpG sites had diverse methylation profiles in obese and lean individuals, one of which was the telomerase catalytic subunit (TERT). In eight of ten cases the methylation change was reverted between obese and lean individuals. One region proved to be differentially methylated with obesity (LINC00304) independent of age. This study provides evidence that obesity influences age driven epigenetic changes, which provides a molecular link between aging and obesity. This link and the identified markers may prove to be valuable biomarkers for the understanding of the molecular basis of aging, obesity and associated diseases. 相似文献
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Vita Rovite Ramona Petrovska Iveta Vaivade Ineta Kalnina Davids Fridmanis Linda Zaharenko Raitis Peculis Valdis Pirags Helgi B. Schioth Janis Klovins 《Molecular biology reports》2014,41(3):1491-1500
Melanocortin 4 receptor (MC4R) is an important regulator of food intake and number of studies report genetic variations influencing the risk of obesity. Here we explored the role of common genetic variation from MC4R locus comparing with SNPs from gene FTO locus, as well as the frequency and functionality of rare MC4R mutations in cohort of 380 severely obese individuals (BMI > 39 kg/m2) and 380 lean subjects from the Genome Database of Latvian Population (LGDB). We found correlation for two SNPs—rs11642015 and rs62048402 in the fat mass and obesity-associated protein (FTO) with obesity but no association was detected for rs17782313 located in the MC4R locus in these severely obese individuals. We sequenced the whole gene MC4R coding region in all study subjects and found five previously known heterozygous non-synonymous substitutions V103I, I121T, S127L, V166I and I251L. Expression in mammalian cells showed that the S127L, V166I and double V103I/S127L mutant receptors had significantly decreased quantity at the cell surface compared to the wild type MC4R. We carried out detailed functional analysis of V166I that demonstrated that, despite low abundance in plasma membrane, the V166I variant has lower EC50 value upon αMSH activation than the wild type receptor, while the level of AGRP inhibition was decreased, implying that V166I cause hyperactive satiety signalling. Overall, this study suggest that S127L may be the most frequent functional MC4R mutation leading to the severe obesity in general population and provides new insight into the functionality of population based variants of the MC4R. 相似文献
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Shields VD Smith KP Arnold NS Gordon IM Shaw TE Waranch D 《Arthropod-Plant Interactions》2008,2(2):101-107
Nine alkaloids (acridine, aristolochic acid, atropine, berberine, caffeine, nicotine, scopolamine, sparteine, and strychnine)
were evaluated as feeding deterrents for gypsy moth larvae (Lymantria dispar (L.); Lepidoptera: Lymantriidae). Our aim was to determine and compare the taste threshold concentrations, as well as the
ED50 values, of the nine alkaloids to determine their potency as feeding deterrents. The alkaloids were applied to disks cut from
red oak leaves (Quercus rubra) (L.), a plant species highly favored by larvae of this polyphagous insect species. We used two-choice feeding bioassays
to test a broad range of biologically relevant alkaloid concentrations spanning five logarithmic steps. We observed increasing
feeding deterrent responses for all the alkaloids tested and found that the alkaloids tested exhibited different deterrency
threshold concentrations ranging from 0.1 to 10 mM. In conclusion, it appears that this generalist insect species bears a
relatively high sensitivity to these alkaloids, which confirms behavioral observations that it avoids foliage containing alkaloids.
Berberine and aristolochic acid were found to have the lowest ED50 values and were the most potent antifeedants.
Handling Editor: Joseph Dickens. 相似文献
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Application of regurgitant from Leptinotarsa decemlineata Say on wound surfaces of one wounded leaf of intact bean (Phaseolus vulgaris L.) plants resulted in activation of ethylene biosynthesis followed by an increase of both peroxidase and polyphenol oxidase activity. The aim of the present investigation was to study the source of increased oxidative enzyme activities in regurgitant-treated bean leaves and to determine if hydrogen peroxide and ethylene biosynthesis is responsible for regurgitant-induced amplification of wound responses in bean plants. As the regurgitant contained relative high activities of both peroxidase and polyphenol oxidase, there is a possibility that increased enzyme activities in bean leaves following regurgitant treatment is an artifact of insect-derived enzymes. Localisation experiments and electrophoretic analysis revealed that only part of the increased enzyme activities could be attributed to regurgitant-derived enzymes. Both increase of ethylene production and oxidative enzyme activities depended on protein synthesis. To demonstrate if the increase of oxidative metabolism was ethylene-dependent, seedlings were pretreated with aminooxyacetic acid, an inhibitor of ethylene biosynthesis, and 1-methylcyclopropene (1-MCP), a competitive inhibitor of ethylene action. Increase of both peroxidase and polyphenol oxidase activity in wounded and subsequently regurgitant-treated leaf was abolished by both aminooxyacetic acid and 1-MCP. Inhibitor studies indicated that H2O2 generated through NADPH oxidase and superoxide dismutase is necessary for regurgitant-induced increase of ethylene production and oxidative enzyme activities. 相似文献
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Juris E. Shvinka Lolita M. Pankova Ineta N. Mežbårde Leons J. Licis 《Applied microbiology and biotechnology》1989,31(3):240-245
Summary The anaerobic aerotolerant bacterium Zymomonas mobilis 113 produced superoxide (O
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) and hydrogen peroxide (H2O2) under aerobic conditions. The main generators of H2O2 were glucose oxidase and superoxide dismutase (SOD). The O
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generation was probably related to minor alternative reduced nicotinamide adenine zinucleotide (NADH)-oxidation reactions in the electron transport chain. An increase in medium pO2 was observed during growth of Z. mobilis 113 in a batch culture. The maximum pO2 increase correlated with glucose oxidase and SOD activities. An decrease in medium pO2 value coincided with an increase in catalase activity in batch culture. Medium deoxygenation reduced the pO2 effect, yet the culture still responded with a pO2 increase after inoculation and addition of the feeding medium. We conclude that the apparent pO2 effects are related to changes in H2O2 concentration in the culture liquid. 相似文献
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Ineta Kalnina Linda Zaharenko Iveta Vaivade Vita Rovite Liene Nikitina-Zake Raitis Peculis Davids Fridmanis Kristine Geldnere Josefin A. Jacobsson Markus S. Almen Valdis Pirags Helgi B. Schiöth Janis Klovins 《Gene》2013
Variations in the FTO gene and near the TMEM18 gene are risk factors for common form of obesity, but have also been linked with type 2 diabetes (T2D). Our aim was to investigate the contribution of these variants to risk of T2D in a population in Latvia. Four single nucleotide polymorphisms (SNP) in the first and fourth intronic regions of FTO and one close to TMEM18 were genotyped in 987 patients with T2D and 1080 controls selected from the Latvian Genome Data Base (LGDB). We confirmed association of SNPs in the first intron (rs11642015, rs62048402 and rs9939609) of FTO and rs7561317 representing the TMEM18 locus with T2D. Association between SNP in FTO and T2D remained significant after correction for body mass index (BMI). The rs57103849 located in the fourth intron of FTO and rs7561317 in TMEM18 showed BMI independent association with younger age at diagnosis of T2D. Our results add to the evidence that BMI related variants in and near FTO and TMEM18 may increase the risk for T2D not only through secondary effects of obesity. The influence of variants in the fourth intron of the FTO gene on development of T2D may be mediated by mechanisms other than those manifested by SNPs in the first intron of the same gene. 相似文献
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Lagerström MC Rabe N Haitina T Kalnina I Hellström AR Klovins J Kullander K Schiöth HB 《Journal of neurochemistry》2007,100(4):1129-1142
The Adhesion family of G protein-coupled receptors (GPCRs) includes 33 receptors and is the second largest GPCR family. Most of these proteins are still orphans and fairly little is known of their tissue distribution and evolutionary context. We report the evolutionary history of the Adhesion family protein GPR123 as well as mapping of GPR123 mRNA expression in mouse and rat using in situ hybridization and real-time PCR, respectively. GPR123 was found to be well conserved within the vertebrate lineage, especially within the transmembrane regions and in the distal part of the cytoplasmic tail, containing a potential PDZ binding domain. The real-time PCR data indicates that GPR123 is predominantly expressed in CNS. The in situ data show high expression in thalamic nuclei and regions containing large pyramidal cells like cortex layers 5 and 6 and subiculum. Moreover, we found distinct expression in amygdala, hypothalamus, inferior olive and spinal cord. The CNS specific expression, together with the high sequence conservation between the vertebrate sequences investigated, indicate that GPR123 may have an important role in the regulation of neuronal signal transduction. 相似文献
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The aim of the experiments reported here was to study possible long-term effects of Neodiprion sertifer Geoff. (Hymenoptera: Diprionidae) herbivory, or artificial defoliation, on oxidative enzyme activities in Scots pine (Pinus sylvestris L.) needles as a consequence of induced defense responses. During year 1 (the first season), defoliation by N. sertifer, which feeds on previous season’s needles, did not result in statistically significant changes in polyphenol oxidase activity
in the current year’s needles. In contrast, defoliation did lead to increased peroxidase activity in those needles. In the
second season (year 2) N. sertifer defoliation of pine seedlings, also defoliated in the previous season either by larvae or artificially, resulted in a decrease
of peroxidase activity in the current year’s needles. No significant differences between treatments carried out in year 1
were found in year 2 for peroxidase activity in the previous year’s needles. However, defoliation in year 1 by N. sertifer resulted in decreased needle consumption, and higher mortality of larvae, in year two. These results indicate the existence
of long-term changes in needle oxidative enzyme activities as a consequence of N. sertifer feeding. 相似文献
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