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61.
62.
Experimental IUGR and later diabetes 总被引:3,自引:0,他引:3
It is widely accepted that an association exists between the intrauterine environment in which a fetus grows and develops and the subsequent development of type 2 diabetes. Any disturbance in maternal ability to provide nutrients and oxygen to the fetus can lead to fetal intrauterine growth restriction (IUGR). Here we will review IUGR in rodent models, in which maternal metabolism has been experimentally manipulated to investigate the molecular basis of the relationship between IUGR and development of type 2 diabetes in later life, and the identification of the molecular derangements in specific metabolically - sensitive organs/tissues. 相似文献
63.
Neutrophil accumulation within epithelial crypts and in the intestinal mucosa directly correlates with clinical disease activity
and epithelial injury in inflammatory bowel disease (IBD). Current advances have defined the mechanisms by which neutrophils
are activated or migrate across endothelial and mucosal epithelial cells. A better understanding of this process will likely
provide new insights into novel treatment strategies for IBD. Especially, activated neutrophils produce reactive oxygen and
nitrogen species and myeloperoxidase within intestinal mucosa, which induce oxidative stress. Posttranslational modification
of proteins generated by these reactive species serves as a “molecular fingerprint” of protein modification by lipid peroxidation-,
nitric oxide-, and myeloperoxidase-derived oxidants. Measurement of these modified proteins may serve both as a quantitative
index of oxidative stress and an important new biological marker of clinical relevance to IBD. We have succeeded in the clinical
development of a novel granulocyte adsorptive apheresis therapy for IBD. In this review, we discuss current advances in defining
the role of neutrophil-dependent oxidative stress in IBD. 相似文献
64.
Groebe K Krause F Kunstmann B Unterluggauer H Reifschneider NH Scheckhuber CQ Sastri C Stegmann W Wozny W Schwall GP Poznanović S Dencher NA Jansen-Dürr P Osiewacz HD Schrattenholz A 《Experimental gerontology》2007,42(9):887-898
According to the 'free radical theory of ageing', the generation and accumulation of reactive oxygen species are key events during ageing of biological systems. Mitochondria are a major source of ROS and prominent targets for ROS-induced damage. Whereas mitochondrial DNA and membranes were shown to be oxidatively modified with ageing, mitochondrial protein oxidation is not well understood. The purpose of this study was an unbiased investigation of age-related changes in mitochondrial proteins and the molecular pathways by which ROS-induced protein oxidation may disturb cellular homeostasis. In a differential comparison of mitochondrial proteins from young and senescent strains of the fungal ageing model Podospora anserina, from brains of young (5 months) vs. older rats (17 and 31 months), and human cells, with normal and chemically accelerated in vitro ageing, we found certain redundant posttranslationally modified isoforms of subunits of ATP synthase affected across all three species. These appear to represent general susceptible hot spot targets for oxidative chemical changes of proteins accumulating during ageing, and potentially initiating various age-related pathologies and processes. This type of modification is discussed using the example of SAM-dependent O-methyltransferase from P. anserina (PaMTH1), which surprisingly was found to be enriched in mitochondrial preparations of senescent cultures. 相似文献
65.
Levental I Lingwood D Grzybek M Coskun U Simons K 《Proceedings of the National Academy of Sciences of the United States of America》2010,107(51):22050-22054
The physical basis for protein partitioning into lipid rafts remains an outstanding question in membrane biology that has previously been addressed only through indirect techniques involving differential solubilization by nonionic detergents. We have used giant plasma membrane vesicles, a plasma membrane model system that phase separates to include an ordered phase enriching for raft constituents, to measure the partitioning of the transmembrane linker for activation of T cells (LAT). LAT enrichment in the raft phase was dependent on palmitoylation at two juxtamembrane cysteines and could be enhanced by oligomerization. This palmitoylation requirement was also shown to regulate raft phase association for the majority of integral raft proteins. Because cysteine palmitoylation is the only lipid modification that has been shown to be reversibly regulated, our data suggest a role for palmitoylation as a dynamic raft targeting mechanism for transmembrane proteins. 相似文献
66.
Post-translational modification of amino acid residues is a common way to regulate localization, stability and ultimately the function of the protein. Tissue factor (TF), the major initiator of blood coagulation cascade, receives several post-translational modifications, like glycosylation, phosphorylation, palmitoylation and nitrosylation. Recent studies have demonstrated that these processes play important roles in modulating biological functions of TF. The present review highlights the mechanisms of several common protein post-translational modifications of TF with the special reference on the recent knowledge about their roles in regulation of trafficking, stability as well as procoagulant and signaling functions of TF. 相似文献
67.
Podoplanin is a small mucin-like transmembrane protein, widely expressed in various specialised cell types throughout the body. Here, we revisit the mechanism of podoplanin-mediated tumour invasion. We compare molecular pathways leading to single and collective cell invasion and discuss novel distinct concepts of tumour cell invasion. 相似文献
68.
Obesity and related complications are major health burdens. Almost 700 million adults are currently obese globally and the prevalence is predicted to rise towards 2030. The sudden change of lifestyle with physical inactivity and excessive calorie intake undoubtedly have a major part of the epidemic development; however, some individuals seem to be more prone to be affected by an unhealthy lifestyle than others. Hence, genetic predisposition also has an essential role in determining disease susceptibility and response to lifestyle factors. Since the introduction of genome-wide association studies (GWAS), the success of identifying obesity susceptibility variants have increased, and a total of 32 variants have been identified associating genome-wide significantly with body mass index (BMI) and 18 with measures of fat distribution during four overall obesity GWAS waves. However, the immediate success of the GWAS approach has eased off, but the proportion of explained variance for BMI by the identified obesity variants remains low. This review suggests and discusses new initiatives to take GWAS of obesity to the next level, including gene–environment interactions as modulating/masking factors, low-frequent or rare variants and ways to address such analyses, and finally reflections about the applicability of epigenetic modifications when elucidating the genetic background of obesity. 相似文献
69.
Kaposi’s sarcoma-associated herpesvirus is an oncogenic γ-herpesvirus that causes latent infection in humans. In cells, the viral genome adopts a highly organized chromatin structure, which is controlled by a wide variety of cellular and viral chromatin regulatory factors. In the past few years, interrogation of the chromatinized KSHV genome by whole genome-analyzing tools revealed that the complex chromatin landscape spanning the viral genome in infected cells has important regulatory roles during the viral life cycle. This review summarizes the most recent findings regarding the role of histone modifications, histone modifying enzymes, DNA methylation, microRNAs, non-coding RNAs and the nuclear organization of the KSHV epigenome in the regulation of latent and lytic viral gene expression programs as well as their connection to KSHV-associated pathogenesis. 相似文献
70.
Abstract: Lactoferricins are a class of antibacterial peptides isolated after gastric‐pepsin digest of the mammalian iron‐chelating‐protein lactoferrin. For investigation of antibacterial activity, we prepared short synthetic derivatives of bovine, human, caprine, murine and porcine lactoferricins with 15‐amino‐acid residues of high sequence homology. The peptides corresponded to amino‐acid residues 17–31 of the mature bovine lactoferrin. Only the bovine and caprine derivatives displayed measurable antibacterial activity, with the bovine one having a minimal inhibitory concentration of 24 µm and being 10 times more active than the caprine one against Escherichia coli. An alanine‐scan of the bovine lactoferricin derivative was performed to identify specific amino acids that were important for the antibacterial activity. We found that neither of the two tryptophan residues (Trp 6 and Trp 8) present in the bovine lactoferricin derivative could be replaced by alanine without a major loss of antibacterial activity. The other lactoferricin derivatives tested contained only one tryptophan residue (Trp 6). Modified human, caprine and porcine lactoferricin derivatives containing two tryptophan residues (Trp 6 and Trp 8) displayed minimal inhibitory concentrations of 74, 174 and 219 µm , respectively, which represented up to a six‐fold increase in antibacterial activity. The alanine‐scan also revealed that the antibacterial activity was increased when acetamidomethyl‐protected cysteine and unprotected glutamine (Cys 3 and Gln 7) were replaced with alanine. Only the bovine lactoferricin derivative and a few of its alanine‐modified derivatives displayed measurable activity against Staphylococcus aureus. 相似文献