Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The xylosyltransferases I and II (XT-I, XT-II, EC 2.4.2.26) catalyze the transfer of xylose from UDP-xylose to selected serine residues in the proteoglycan core protein, which is the initial and ratelimiting step in glycosaminoglycan biosynthesis. Both xylosyltransferases are Golgi-resident enzymes and transfer xylose to similar core proteins acceptors. XT-I and XT-II are differentially expressed in cell types and tissues, although the reason for the existence of two xylosyltransferase isoforms in all higher organisms remains elusive. Serum xylosyltransferase activity was found to be a biochemical marker for the assessment of disease activity in systemic sclerosis and for the diagnosis of fibrotic remodeling processes. Furthermore, sequence variations in the XT-I and XT-II coding genes were identified as risk factors for diabetic nephropathy, osteoarthritis or pseudoxanthoma elasticum. These findings point to the important role of the xylosyltransferases as disease modifiers in pathologies which are characterized by an altered proteoglycan metabolism. The present review discusses recent advances in mammalian xylosyltransferases and the impact of xylosyltransferases in proteoglycan-associated diseases.
Cell Mol Life Sci 2007 Jun
PMID:Human xylosyltransferases in health and disease. 1743 56

Heparan sulfate (HS) is a member of the family of glycosaminoglycans (GAGs) that is generally bound to a core protein to form a proteoglycan (PG). HSPGs may be cell-membrane associated (glypicans and syndecans) or located within the extracellular matrix (agrin, perlecan and type XVIII collagen). The sulfate and carboxylic groups in HS are responsible for the negative charge of the sugar chain. HS is abundantly present in the filter unit of the kidney, especially in the glomerular basement membrane (GBM), and is assumed to repel negatively charged proteins, including albumin, thereby preventing their filtration. Alterations in HS expression in the GBM have been reported in a number of renal pathologies, including diabetic nephropathy, minimal change nephropathy and membranous glomerulopathy.A decreased HS expression in the GBM generally correlates with an increase in the level of proteinuria. Progressive proteinuria may result in end-stage renal failure when untreated. Based on these findings, GAG-based drugs have been used to treat proteinuria and some, notably sulodexide, have shown beneficial effects. The biosynthesis of HS and its possible role in renal filtration are discussed, an overview of GAG-based drugs and their effect on proteinuria is provided, and possible mechanisms by which GAG-based drugs ameliorate proteinuria are discussed.
Curr Opin Mol Ther 2007 Aug
PMID:Anti-proteinuric effects of glycosaminoglycan-based drugs. 1769 49

This review briefly handles the use of (1)H NMR spectroscopy in lipoprotein subclass analytics. Potential diagnostic uses of (1)H NMR metabonomics of human serum for coronary heart disease, diabetic nephropathy and cancer are also discussed. In addition, miscellaneous recent applications of NMR metabonomics (e.g., a pharmacometabonomic tactic to personalize drug treatment) as well as multi-organ, multispecies and multi-omics approaches to molecular systems biology are featured. Some related experimental and data analysis methodologies are briefly introduced with respect to the biochemical rationales. Critical considerations on the potential diagnostic value of in vitro (1)H NMR are presented together with optimism toward the usage of body fluid (1)H NMR metabonomics in disease risk assessment and as an aid for personalized medicine.
Expert Rev Mol Diagn 2007 Nov
PMID:Potential role of body fluid 1H NMR metabonomics as a prognostic and diagnostic tool. 1802 Sep 6

Two (pro)renin receptors have been characterized so far, the mannose-6-phosphate receptor (M6P-R) and a specific receptor called (P)RR for (pro)renin receptor. Each receptor controls a different aspect of renin and prorenin metabolism. The M6P-R is a clearance receptor, whereas (P)RR mediates their cellular effects by activating intracellular signaling and up-regulating gene expression. Moreover, binding to (P)RR increases renin enzymatic activity and fully activates prorenin, the inactive proenzyme form of renin. Experimental models suggest that increased (P)RR synthesis and/or activation may be relevant to diseases, especially to high blood pressure, to cardiac fibrosis associated with hypertension, and to diabetic nephropathy.
J Mol Med (Berl) 2008 Jun
PMID:The (pro)renin receptors. 1832 68

As is diabetes itself, diabetic angiopathy is a multi-factorial disease. Advanced glycation endproducts (AGE) cause vascular cell derangement characteristic of diabetes, and this is mainly mediated by their interaction with receptor for AGE (RAGE). When made diabetic, RAGE-overexpressing transgenic mice exhibited exacerbation of the indices of nephropathy, and this was prevented by the inhibition of AGE formation. On the other hand, RAGE-deficient animals showed amelioration of diabetic nephropathy. Accordingly, AGE and RAGE should be regarded as environmental and cellular accounts and as a potential therapeutic target for diabetic nephropathy. In effect, substances that inhibit the formation of AGE, break preformed AGE, change metabolic flows away from glycation, antagonize RAGE, and capture RAGE ligands have been proven as effective remedies against this life-threatening disease.
Curr Mol Med 2007 Dec
PMID:RAGE in diabetic nephropathy. 1833 Dec 33

For many years, angiotensin II with its respective receptors was considered to be the only effector molecule within the renin-angiotensin system. Nevertheless, several studies indicated that renin (the enzyme catalyzing the generation of angiotensin I) and its enzymatically inactive precursor prorenin may have an angiotensin-II-independent (patho)physiological significance. In 2002, a specific (pro)renin receptor ((P)RR)) which increases the enzymatic activity of its ligands and induces an intrinsic activity upon ligand binding has been published. Recently, our group has demonstrated a novel (P)RR signal transduction pathway involving direct protein-protein interaction between the (P)RR and the transcription factor promyelocytic zinc finger protein (PLZF) and the nuclear translocation of PLZF upon renin stimulation. Downstream effects of (P)RR activation by renin included repression of the (P)RR itself and induction of the p85alpha subunit of the phosphatidylinositol-3 kinase (PI3K-p85alpha) as well as an increase in proliferation and a decrease in apoptotic activity. Various animal models demonstrated that inhibition of prorenin binding to the (P)RR can prevent or even abolish the development of cardiac fibrosis and diabetic nephropathy via angiotensin-II-independent mechanisms. Additional studies that verify these remarkable findings are needed. Moreover, the potency of aliskiren (the first orally active renin inhibitor in the market) to interfere with a putatively detrimental binding of (pro)renin to the (P)RR is of particular interest and has to be elucidated.
J Mol Med (Berl) 2008 Jun
PMID:PLZF and the (pro)renin receptor. 1833 87

Urinary 8-hydroxy-2'-deoxyguanosine (8OHdG) is an excellent marker of oxidative DNA damage. Until now, urinary 8OHdG has been measured by high-performance liquid chromatography with electrochemical detection. A simple and sensitive method for the analysis of urinary 8OHdG by capillary electrophoresis with end-column amperometric detection has been developed and is described in this chapter. A single-step solid-phase extraction procedure was optimized and used for extracting 8OHdG from human urine. To improve the sensitivity of this method, a new focusing technique based on a dynamic pH junction was used. In the end, the urinary concentration of 8OHdG in healthy persons, patients with cancer, patients with diabetic nephropathy, and smokers was determined. Emphasis is focused on the establishment and application of the methods.
Methods Mol Biol 2008
PMID:Capillary electrophoresis of oxidative DNA damage. 1839 78

Endothelial dysfunction plays a key role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy. Endothelial-derived nitric oxide synthase (eNOS) gene polymorphisms affect eNOS activity and are associated with endothelial dysfunction. We evaluated the association of the constitutive endothelial nitric oxide synthase gene (eNOS) polymorphisms with type 2 diabetic nephropathy. We genotyped three polymorphisms of eNOS (Two SNPs: -786T > C, 894G > T and one 27-bp repeat polymorphism in Intron 4 (27VNTR)) in type 2 diabetic nephropathy patients (cases: n = 195) and type 2 diabetic without nephropathy (controls: n = 255), using validated PCR-RFLP assays. We measured serum NO levels in these subjects and examined its correlation with diabetic nephropathy and eNOS genotypes. The frequency of CC (-786T > C), TT (894G > T) and aa genotypes (27VNTR) were significantly higher in diabetic nephropathy patients as compared to the diabetes without nephropathy group (CC: P = 0.003, TT: P = 0.03, aa: P < 0.0001). These mutant genotypes were found to be associated with higher risk of nephropathy (-786T > C: OR: 5.5, 95%CI: 1.53-19.79; 894G > T: OR: 1.8, 95%CI: 1.03-3.16; Intron 4: OR: 6.23, 95%CI: 2.23-16.31). Haplotype with all the wild alleles (T-b-G) was found to be associated with a decreased risk of nephropathy (OR: 0.68, P = 0.005) and haplotype with all mutant alleles (C-a-T) was associated with higher risk of diabetic nephropathy as compared to diabetes without nephropathy group (OR: 2.6, P = 0.14). No significant linkage disequilibria were observed among the variants in this case-control study. The serum NO levels were observed to be significantly (P < 0.05) lower in mutant allele carriers ('C' allele of T-786C SNP and/or 'T' allele of G894T SNP) as compared with the wild-type allele carriers (-786T and/or 894G) within each of the subject groups (with and without nephropathy). These results suggest that the eNOS gene locus is associated with diabetic nephropathy and the functional polymorphisms (-786T > C & 894G > T) might lead to a decreased expression of eNOS gene.
Mol Cell Biochem 2008 Jul
PMID:Endothelial nitric oxide synthase gene haplotypes and diabetic nephropathy among Asian Indians. 1840 56

Association between the (AC)(n) dinucleotide repeat polymorphism at the 5'-end of the aldose reductase gene and the occurrence of diabetic nephropathy was conducted. We examined eight studies consisting of ten Caucasian type 1 diabetes mellitus case-control comparisons and eight studies consisting of nine type 2 diabetes mellitus case-control comparisons, which were based on our inclusion criterion and available in the literature. The meta-analysis demonstrated a large heterogeneity among the studies on the type 1 diabetic subjects and a significant association was observed between the (AC)(n) dinucleotide repeat polymorphism at the 5'-end of the aldose reductase gene and diabetic nephropathy. The Z-2 allele appeared to be a genetic risk factor for susceptibility to diabetic nephropathy with a random effects odds ratio (OR) of 1.40 (95% confidence interval, CI (1.07, 1.84)). The Z+2 allele showed a protective effect on diabetic nephropathy with a random effects OR of 0.77 (95% CI (0.65, 0.91)). The meta-analysis, however, showed no association between the genetic polymorphism and diabetic nephropathy in type 2 diabetic subjects. Neither the risk Z-2 allele nor the protective Z+2 allele in type 1 diabetic subjects appeared to have an effect on nephropathy in type 2 diabetic subjects, while their fixed effects OR was 1.09 (95% CI (0.96, 1.22)) and 0.88 (95% CI (0.67, 1.15)) respectively. The current meta-analysis demonstrated a correlation between the (AC)(n) dinucleotide repeat polymorphism and the occurrence of diabetic nephropathy in Caucasian type 1 diabetic subjects in contrast to type 2 diabetic subject population in which such an association could not be demonstrated.
J Mol Endocrinol 2008 May
PMID:Association between (AC)n dinucleotide repeat polymorphism at the 5'-end of the aldose reductase gene and diabetic nephropathy: a meta-analysis. 1843 30

The inhibition of the renin-angiotensin system is one of the most commonly utilized ways to lower blood pressure in patients with arterial hypertension. Up till now, angiotensin-converting enzyme inhibitors as well as angiotensin receptor blockers are the established inhibitors of this system, and both classes are used in clinical routine. There is a wealth of information about those classes, which are known not only to lower blood pressure, but also to prevent end-organ damage and, ultimately, reduce mortality in patients. Direct renin inhibition was already targeted 30 years ago to inhibit the renin-angiotensin system, but low bioavailability and short duration of action of the first generations of renin inhibitors withheld their clinical success. With the new generation of non-peptide orally available renin inhibitors, a third substance to inhibit the renin-angiotensin system is on the market, and the prototype of this class, aliskiren, has now been tested in various clinical trials in arterial hypertension. We review the studies of aliskiren and discuss its current role in the contemporary treatment of arterial hypertension as well as the possible new fields of action for aliskiren in treating heart failure and diabetic nephropathy.
J Mol Med (Berl) 2008 Jun
PMID:Renin inhibitors, clinical experience. 1843 34


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