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Alba Casellas Cristina Mallol Ariana Salavert Veronica Jimenez Miquel Garcia Judith Agudo Mercè Obach Virginia Haurigot Laia Vilà Maria Molas Ricardo Lage Meritxell Morró Estefania Casana Jesús Ruberte Fatima Bosch 《The Journal of biological chemistry》2015,290(27):16772-16785
The human insulin-like growth factor 2 (IGF2) and insulin genes are located within the same genomic region. Although human genomic studies have demonstrated associations between diabetes and the insulin/IGF2 locus or the IGF2 mRNA-binding protein 2 (IGF2BP2), the role of IGF2 in diabetes pathogenesis is not fully understood. We previously described that transgenic mice overexpressing IGF2 specifically in β-cells (Tg-IGF2) develop a pre-diabetic state. Here, we characterized the effects of IGF2 on β-cell functionality. Overexpression of IGF2 led to β-cell dedifferentiation and endoplasmic reticulum stress causing islet dysfunction in vivo. Both adenovirus-mediated overexpression of IGF2 and treatment of adult wild-type islets with recombinant IGF2 in vitro further confirmed the direct implication of IGF2 on β-cell dysfunction. Treatment of Tg-IGF2 mice with subdiabetogenic doses of streptozotocin or crossing these mice with a transgenic model of islet lymphocytic infiltration promoted the development of overt diabetes, suggesting that IGF2 makes islets more susceptible to β-cell damage and immune attack. These results indicate that increased local levels of IGF2 in pancreatic islets may predispose to the onset of diabetes. This study unravels an unprecedented role of IGF2 on β-cells function. 相似文献
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Jorge Vera-Otarola Estefania Castillo-Vargas Jenniffer Angulo Francisco M. Barriga Eduard Batlle Marcelo Lopez-Lastra 《PLoS pathogens》2021,17(9)
The capped Small segment mRNA (SmRNA) of the Andes orthohantavirus (ANDV) lacks a poly(A) tail. In this study, we characterize the mechanism driving ANDV-SmRNA translation. Results show that the ANDV-nucleocapsid protein (ANDV-N) promotes in vitro translation from capped mRNAs without replacing eukaryotic initiation factor (eIF) 4G. Using an RNA affinity chromatography approach followed by mass spectrometry, we identify the human RNA chaperone Mex3A (hMex3A) as a SmRNA-3’UTR binding protein. Results show that hMex3A enhances SmRNA translation in a 3’UTR dependent manner, either alone or when co-expressed with the ANDV-N. The ANDV-N and hMex3A proteins do not interact in cells, but both proteins interact with eIF4G. The hMex3A–eIF4G interaction showed to be independent of ANDV-infection or ANDV-N expression. Together, our observations suggest that translation of the ANDV SmRNA is enhanced by a 5’-3’ end interaction, mediated by both viral and cellular proteins. 相似文献
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Emily A. Hu Estefania Toledo Javier Diez-Espino Ramon Estruch Dolores Corella Jordi Salas-Salvado Ernest Vinyoles Enrique Gomez-Gracia Fernando Aros Miquel Fiol Jose Lapetra Lluis Serra-Majem Xavier Pintó Maria Puy Portillo Rosa M. Lamuela-Raventos Emilio Ros Jose V. Sorli Miguel A. Martinez-Gonzalez 《PloS one》2013,8(4)
Background
The traditional Mediterranean dietary pattern (MedDiet) is associated with longevity and low rates of cardiovascular disease (CVD). However, there is little information on who is more likely to follow this food pattern.Aim
To evaluate how different factors are associated with lower MedDiet adherence in older Spanish subjects.Methods
We included 7305 participants (men aged 55–80 y, women 60–80 y) at high-risk of CVD recruited into the PREDIMED trial (ISRCTN35739639). Socioeconomic, anthropometric, lifestyle characteristics and CVD risk factors were recorded. A validated 14-item questionnaire was used to evaluate MedDiet adherence at baseline. Multivariate models were used to estimate odds ratios (OR) and 95% confidence intervals for lower adherence to the MedDiet (<9 points out of 14) and ascertain factors independently associated with it.Results
Former smoking (OR = 0.87; 95% CI, 0.78–0.98), physical activity (OR for the 3rd vs. the 1sttertile: 0.69; 0.62–0.78), and higher educational level (OR for university vs. less than primary school: 0.54; 0.38–0.77) were associated with higher MedDiet adherence. Conversely, having a larger waist-to-height ratio (OR for 0.1 units, 1.35; 1.22–1.49), being diabetic (OR = 1.13; 1.03–1.24), being single (OR = 1.27; 1.01–1.61) or divorced or separated (OR = 1.44; 1.09–1.89), and current smoking (OR = 1.28; 1.11–1.47) were associated with lower adherence.Conclusions
Participants with little education, a larger waist-to-height ratio, or diabetes and those who were less physically active, single, divorced or separated, or smokers were less likely to adhere to the MedDiet, an ideal model for food choices. Stronger efforts of health promotion are needed in these groups to foster adoption of the MedDiet. 相似文献56.
As survival of mouse oocytes subjected to vitrification depends far more on the warming rate than on the cooling rate, we wished to determine whether the lack of correlation between survival and cooling rate was mirrored by a lack of correlation between cooling rate and vitrification of the medium (EAFS), and between survival and the vitrification of the medium. The morphological and functional survival of the oocytes showed little or no relation to whether or not the EAFS medium vitrified or froze. We studied if the droplet size and the elapsed time (between placing the droplet on the Cryotop and the start of cooling) affects the result through modification of the cooling rate and solute concentration. Dehydration was rapid; consequently, the time between the placing the droplets into a Cryotop and cooling must be held to a minimum. The size of the EAFS droplet that is being cooled does not seem to affect vitrification. Finally, the degree to which samples of EAFS vitrify is firmly dependent on both its solute concentration and the cooling rate. 相似文献
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Magali de Bruyn Jennifer Vandooren Estefania Ugarte-Berzal Ingrid Arijs Séverine Vermeire 《Critical reviews in biochemistry and molecular biology》2016,51(5):295-358
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be predominant proteases and protease inhibitors involved in the pathogenesis of inflammatory bowel diseases (IBD) through their ability to remodel the extracellular matrix (ECM) in response to inflammatory stimuli and by their immunomodulating effects. An imbalance between MMPs and TIMPs has been linked with acute and chronic inflammation and aberrant tissue remodeling, as seen in IBD. Moreover, recurrent phases of tissue destruction and subsequent tissue repair can cause serious complications in IBD patients such as fistulas and fibrosis. The aims of this review are (i) to summarize current literature on genetic association, mRNA, and protein expression studies with regard to MMPs and TIMPs in IBD patients and various animal models, including those with transgenic and knockout mice; (ii) to compare biochemical and molecular biological data in humans with those obtained in animal model studies and (iii) to critically evaluate and translate how this knowledge may be used in practical terms to understand better the pathophysiology and mechanisms operating in IBD and to apply this for improvement of clinical outcomes at diagnostic, prognostic and therapeutic levels. 相似文献