排序方式: 共有114条查询结果,搜索用时 15 毫秒
71.
Jose Gomez Pilar Caro Ines Sanchez Alba Naudi Mariona Jove Manuel Portero-Otin Monica Lopez-Torres Reinald Pamplona Gustavo Barja 《Journal of bioenergetics and biomembranes》2009,41(3):309-321
Methionine restriction without energy restriction increases, like caloric restriction, maximum longevity in rodents. Previous
studies have shown that methionine restriction strongly decreases mitochondrial reactive oxygen species (ROS) production and
oxidative damage to mitochondrial DNA, lowers membrane unsaturation, and decreases five different markers of protein oxidation
in rat heart and liver mitochondria. It is unknown whether methionine supplementation in the diet can induce opposite changes,
which is also interesting because excessive dietary methionine is hepatotoxic and induces cardiovascular alterations. Because
the detailed mechanisms of methionine-related hepatotoxicity and cardiovascular toxicity are poorly understood and today many
Western human populations consume levels of dietary protein (and thus, methionine) 2–3.3 fold higher than the average adult
requirement, in the present experiment we analyze the effect of a methionine supplemented diet on mitochondrial ROS production
and oxidative damage in the rat liver and heart mitochondria. In this investigation male Wistar rats were fed either a L-methionine-supplemented
(2.5 g/100 g) diet without changing any other dietary components or a control (0.86 g/100 g) diet for 7 weeks. It was found
that methionine supplementation increased mitochondrial ROS generation and percent free radical leak in rat liver mitochondria
but not in rat heart. In agreement with these data oxidative damage to mitochondrial DNA increased only in rat liver, but
no changes were observed in five different markers of protein oxidation in both organs. The content of mitochondrial respiratory
chain complexes and AIF (apoptosis inducing factor) did not change after the dietary supplementation while fatty acid unsaturation
decreased. Methionine, S-AdenosylMethionine and S-AdenosylHomocysteine concentration increased in both organs in the supplemented
group. These results show that methionine supplementation in the diet specifically increases mitochondrial ROS production
and mitochondrial DNA oxidative damage in rat liver mitochondria offering a plausible mechanism for its hepatotoxicity. 相似文献
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73.
Laia Hernández Mariona Terradas Jordi Camps Marta Martín Laura Tusell Anna Genescà 《Aging cell》2015,14(2):153-161
Aging involves a deterioration of cell functions and changes that may predispose the cell to undergo an oncogenic transformation. The carcinogenic risks following radiation exposure rise with age among adults. Increasing inflammatory response, loss of oxidant/antioxidant equilibrium, ongoing telomere attrition, decline in the DNA damage response efficiency, and deleterious nuclear organization are age‐related cellular changes that trigger a serious threat to genomic integrity. In this review, we discuss the mechanistic interplay between all these factors, providing an integrated view of how they contribute to the observed age‐related increase in radiation sensitivity. As life expectancy increases and so it does the medical intervention, it is important to highlight the benefits of radiation protection in the elderly. Thus, a deep understanding of the mechanistic processes confining the threat of aging‐related radiosensitivity is currently of foremost relevance. 相似文献
74.
Julie Guillermet-Guibert Lee B. Smith Guillaume Halet Maria A. Whitehead Wayne Pearce Diane Rebourcet Kelly León Pascale Crépieux Gemma Nock Maria Str?mstedt Malin Enerback Claude Chelala Mariona Graupera John Carroll Sabina Cosulich Philippa T. K. Saunders Ilpo Huhtaniemi Bart Vanhaesebroeck 《PLoS genetics》2015,11(7)
The organismal roles of the ubiquitously expressed class I PI3K
isoform p110β remain largely unknown. Using a new kinase-dead
knockin mouse model that mimics constitutive pharmacological inactivation of p110β, we document that full inactivation of p110β leads to embryonic lethality in a substantial fraction of mice. Interestingly, the homozygous p110β kinase-dead mice that survive into adulthood (maximum ~26% on a mixed genetic background) have no apparent phenotypes, other than subfertility in females and complete infertility in males. Systemic inhibition of p110β results in a highly specific blockade in the maturation of spermatogonia to spermatocytes. p110β was previously suggested to signal downstream of the c-kit tyrosine kinase receptor in germ cells to regulate their proliferation and survival. We now report that p110β also plays a germ cell-extrinsic role in the Sertoli cells (SCs) that support the developing sperm, with p110β inactivation dampening expression of the SC-specific Androgen Receptor (AR) target gene Rhox5, a homeobox gene critical for spermatogenesis. All extragonadal androgen-dependent functions remain unaffected by global p110β inactivation. In line with a crucial role for p110β in SCs, selective inactivation of p110β in these cells results in male infertility. Our study is the first documentation of the involvement of a signalling enzyme, PI3K, in the regulation of AR activity during spermatogenesis. This developmental pathway may become active in prostate cancer where p110β and AR have previously been reported to functionally interact. 相似文献
75.
Cuezva S Fernandez-Cortes A Porca E Pašić L Jurado V Hernandez-Marine M Serrano-Ortiz P Hermosin B Cañaveras JC Sanchez-Moral S Saiz-Jimenez C 《FEMS microbiology ecology》2012,81(1):281-290
The walls and ceiling of Altamira Cave, northern Spain, are coated with different coloured spots (yellow, white and grey). Electron microscopy revealed that the grey spots are composed of bacteria and bioinduced CaCO(3) crystals. The morphology of the spots revealed a dense network of microorganisms organized in well-defined radial and dendritic divergent branches from the central area towards the exterior of the spot, which is coated with overlying spheroidal elements of CaCO(3) and CaCO(3) nest-like aggregates. Molecular analysis indicated that the grey spots were mainly formed by an unrecognized species of the genus Actinobacteria. CO(2) efflux measurements in rocks heavily covered by grey spots confirmed that bacteria-forming spots promoted uptake of the gas, which is abundant in the cave. The bacteria can use the captured CO(2) to dissolve the rock and subsequently generate crystals of CaCO(3) in periods of lower humidity and/or CO(2). A tentative model for the formation of these grey spots, supported by scanning electron microscopy and transmission electron microscopy data, is proposed. 相似文献
76.
Fay?al Guedj Catherine Sébrié Isabelle Rivals Aurelie Ledru Evelyne Paly Jean C. Bizot Desmond Smith Edward Rubin Brigitte Gillet Mariona Arbones Jean M. Delabar 《PloS one》2009,4(2)
Individuals with partial HSA21 trisomies and mice with partial MMU16 trisomies containing an extra copy of the DYRK1A gene present various alterations in brain morphogenesis. They present also learning impairments modeling those encountered in Down syndrome. Previous MRI and histological analyses of a transgenic mice generated using a human YAC construct that contains five genes including DYRK1A reveal that DYRK1A is involved, during development, in the control of brain volume and cell density of specific brain regions. Gene dosage correction induces a rescue of the brain volume alterations. DYRK1A is also involved in the control of synaptic plasticity and memory consolidation. Increased gene dosage results in brain morphogenesis defects, low BDNF levels and mnemonic deficits in these mice. Epigallocatechin gallate (EGCG) — a member of a natural polyphenols family, found in great amount in green tea leaves — is a specific and safe DYRK1A inhibitor. We maintained control and transgenic mice overexpressing DYRK1A on two different polyphenol-based diets, from gestation to adulthood. The major features of the transgenic phenotype were rescued in these mice. 相似文献
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Christina Ginkel Dieter Hartmann Katharina vom Dorp Armin Zlomuzica Hany Farwanah Matthias Eckhardt Roger Sandhoff Joachim Degen Mariona Rabionet Ekrem Dere Peter D?rmann Konrad Sandhoff Klaus Willecke 《The Journal of biological chemistry》2012,287(50):41888-41902
Ceramide synthase 1 (CerS1) catalyzes the synthesis of C18 ceramide and is mainly expressed in the brain. Custom-made antibodies to a peptide from the C-terminal region of the mouse CerS1 protein yielded specific immunosignals in neurons but no other cell types of wild type brain, but the CerS1 protein was not detected in CerS1-deficient mouse brains. To elucidate the biological function of CerS1-derived sphingolipids in the brain, we generated CerS1-deficient mice by introducing a targeted mutation into the coding region of the cers1 gene. General deficiency of CerS1 in mice caused a foliation defect, progressive shrinkage, and neuronal apoptosis in the cerebellum. Mass spectrometric analyses revealed up to 60% decreased levels of gangliosides in cerebellum and forebrain. Expression of myelin-associated glycoprotein was also decreased by about 60% in cerebellum and forebrain, suggesting that interaction and stabilization of oligodendrocytic myelin-associated glycoprotein by neuronal gangliosides is due to the C18 acyl membrane anchor of CerS1-derived precursor ceramides. A behavioral analysis of CerS1-deficient mice yielded functional deficits including impaired exploration of novel objects, locomotion, and motor coordination. Our results reveal an essential function of CerS1-derived ceramide in the regulation of cerebellar development and neurodevelopmentally regulated behavior. 相似文献
79.
Leanne K. Küpers Sílvia Fernndez-Barrs Aayah Nounu Chloe Friedman Ruby Fore Giulia Mancano Dana Dabelea Sheryl L. Rifas-Shiman Rosa H. Mulder Emily Oken Laura Johnson Mariona Bustamante Vincent W.V. Jaddoe Marie-France Hivert Anne P. Starling Jeanne H.M. de Vries Gemma C. Sharp Martine Vrijheid Janine F. Felix 《Epigenetics》2022,17(11):1419
80.
Morales E Bustamante M Gonzalez JR Guxens M Torrent M Mendez M Garcia-Esteban R Julvez J Forns J Vrijheid M Molto-Puigmarti C Lopez-Sabater C Estivill X Sunyer J 《PloS one》2011,6(2):e17181