1,721,009 research outputs found
Peroxisomes and Kidney Injury
No full textSignificance: Peroxisomes are organelles present in most eukaryotic cells. The organs with the highest density of peroxisomes are the liver and kidneys. Peroxisomes possess more than fifty enzymes and fulfill a multitude of biological tasks. They actively participate in apoptosis, innate immunity, and inflammation. In recent years, a considerable amount of evidence has been collected to support the involvement of peroxisomes in the pathogenesis of kidney injury. Recent Advances: The nature of the two most important peroxisomal tasks, beta-oxidation of fatty acids and hydrogen peroxide turnover, functionally relates peroxisomes to mitochondria. Further support for their communication and cooperation is furnished by the evidence that both organelles share the components of their division machinery. Until recently, the majority of studies on the molecular mechanisms of kidney injury focused primarily on mitochondria and neglected peroxisomes. Critical Issues: The aim of this concise review is to introduce the reader to the field of peroxisome biology and to provide an overview of the evidence about the contribution of peroxisomes to the development and progression of kidney injury. The topics of renal ischemia-reperfusion injury, endotoxin-induced kidney injury, diabetic nephropathy, and tubulointerstitial fibrosis, as well as the potential therapeutic implications of peroxisome activation, are addressed in this review. Future Directions: Despite recent progress, further studies are needed to elucidate the molecular mechanisms induced by dysfunctional peroxisomes and the role of the dysregulated mitochondria-peroxisome axis in the pathogenesis of renal injury
Dysfunctional lysosomal autophagy leads to peroxisomal oxidative burnout and damage during endotoxin-induced stress
No full textMammalian peroxisomes are ubiquitous organelles that possess a comprehensive ensemble of more than 50 enzymes. Cells regulate the number of organelles through dynamic interplay between biogenesis and degradation. Under basal conditions, approximately 30% of the peroxisomal pool is turned over daily. Recycling of peroxisomes is necessary for preservation of their functional competence, and correctly functioning autophagic/lysosomal pathways play a central role. In this study, we investigated (1) how lipopolysaccharide (LPS) influences peroxisomal dynamics and functions; and (2) how a superimposed lysosomal dysfunction affects pexophagy and modifies peroxisomal responses to LPS. We demonstrated that a transiently increased autophagic degradation of peroxisomes, pexophagy, followed by increased proliferation of peroxisomes is a default response to endotoxic stress. Impairment of autophagy due to lysosomal dysfunction, however, abolishes the above peroxisomal dynamics and results in accumulation of functionally compromised peroxisomes. These exhibit an imbalance between preserved hydrogen peroxide (H2O2)-generating acyl-CoA oxidase (ACOX) and dysfunctional/inactivated catalase (CAT), which leads to intra-peroxisomal redox disequilibrium. This metabolic-oxidative mismatch causes further worsening of peroxisomal functions, peroxisomal burnout, with the consequence of enhanced oxidative stress and aggravated organ injury.NIDDK NIH HHS [R01 DK045462, R01 DK084394
Basic fibroblast growth factor (FGF-2) expression is strongly upregulated in human diabetic nephropathy and mediates hyperglycemia induced proliferation in cortical fibroblasts.
No full textOral health-related quality of life in patients on chronic haemodialysis and after kidney transplantation
No full textObjectivesThe objective of the study was to evaluate oral health-related quality of life (OHRQoL) depending on dental and periodontal situation in patients on haemodialysis (HD) and after kidney transplantation (KTx) compared to healthy controls (HC). Subjects and MethodsOHRQoL was assessed using the German short form of Oral Health Impact Profile (OHIP G14). Dental health was estimated using the decayed, missing and filled teeth index (DMF-T). Periodontal health was classified as healthy/mild or moderate/severe periodontitis. Statistical analysis: Mann-Whitney U-test, Kruskal-Wallis test, chi-square test and Fisher's test. ResultsEighty-seven HD patients, 39 KTx patients and 91 HC were included. Significant differences in DMF-T, D-T, M-T and F-T scores were identified between groups (P<0.001). The prevalence of moderate/severe periodontitis was significantly higher in the HD and KTx group compared to HC (P=0.002). Differences in OHIP G14 between groups were neither clinical relevant nor statistically significant (P=0.199). A significant effect of DMF-T (P=0.012), M-T (P<0.001) and periodontitis (P=0.023) on the OHIP G14 scores was identified only in HC. ConclusionsImprovement in dental care of HD and KTx patients is required. OHIP G14 values provide a subjectively considered low importance of oral health in HD and KTx patients, leading to need of motivation and sensitisation of these patients
Comparative Serum Proteomic Analysis of Differentially Regulated Proteins in Patients with Rheumatoid Arthritis and Healthy Volunteers
No full textBackground: To identify differentially regulated serum proteins, we compared proteome profiles of sera from patients with rheumatoid arthritis (RA) and healthy controls using proteomics. Methods: Sera were collected from 43 patients with RA and 48 healthy volunteers. The samples were cleared of the most abundant major proteins by immunoaffinity chromatography. Serum protein profiles between the two groups were compared by two-dimensional differential gel electrophoresis (2D-DIGE) and differentially regulated proteins were studied using mass spectrometry. Results: We identified 26 differentially expressed serum proteins between patients with RA and healthy controls. A quantitatively significant change of protein levels was defined as at least 1.5-fold upregulation or 0.6-fold downregulation respectively. Using these criteria, patients with RA exhibited significantly higher levels of leucine-rich alpha-2-glycoprotein (p<0.01), apolipoprotein A-IV (p<0.001), clusterin (p<0.001), haptoglobin (p<0.001), Ig alpha-1 chain C region (p<0.05), retinol-binding protein 4 (p<0.001), serum amyloid A (p<0.01) and alpha-1-antichymotrypsin (p<0.01). The levels of serotransferrin were significantly decreased in RA patients (p<0.01). Conclusion: We identified eight proteins with significantly increased and one protein with significantly decreased serum levels in RA patients compared to healthy controls. Several of these proteins may be implicated in the pathogenesis of RA and may have potential in diagnostics and activity assessment of RA
Hyperglycemia induces the expression of basic fibroblast growth factor (FGF-2) through activation of the protein kinase C beta-1 and p65 nf-kappa b in human renal fibroblasts
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