Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To gain insight into the glomerular capillary repair mechanisms in immunoglobulin A (IgA) nephropathy, we focused on vascular endothelial growth factor (VEGF-A) and nitric oxide (NO). Because abnormal glycosylation of serum IgA has been shown in IgA nephropathy, we examined whether VEGF-A and NO production by mesangial cells (MCs) could be modulated by aberrantly glycosylated (desialylated or degalactosylated) IgA. VEGF-A and NO synthase (NOS) gene expression were examined by reverse-transcriptase polymerase chain reaction (RT-PCR) or Northern blot analysis, and VEGF-A peptide, by capture enzyme-linked immunosorbent assay and NOS activity as production of tritium ([(3)H]) citrulline from [(3)H] arginine. Semiquantitative densitometric analysis of RT-PCR experiments showed a significant downregulation of VEGF-A messenger RNA (mRNA) in MCs incubated with aberrantly glycosylated IgA. This resulted in decreased release of VEGF-A in culture medium (P: < 0. 01). NOS activity and inducible NOS (iNOS) mRNA were enhanced by aberrantly glycosylated IgA (both P: < 0.01). No modulation of constitutive NOS mRNA was found. The depression of the VEGF-A production induced by aberrantly glycosylated IgA was mediated by NO because it was completely reversed by the NOS inhibitor, N:omega-nitro-L-arginine methyl ester. The NO donor, sodium nitroprusside, induced a bimodal modulation of VEGF; although low concentrations (0.0001 nmol/L) increased VEGF-A synthesis, greater concentrations (1,000 nmol/L) depressed it. In conclusion, we report negative control of VEGF-A synthesis in MCs by aberrantly glycosylated IgA, mediated by enhanced iNOS activity. We speculate that both increased iNOS activity and depressed VEGF-A synthesis might have a role in impairing vascular repair and favor sclerosis in IgA nephropathy.
 ...
PMID:Aberrantly glycosylated IgA molecules downregulate the synthesis and secretion of vascular endothelial growth factor in human mesangial cells. 1109 49

It is known that aberrant sialylation of IgA1 is involved in the pathogenesis of IgA nephropathy (IgAN). We hypothesize that aberrant sialylation of serum IgA1 may result from changes in the activity of alpha2,6-sialyltransferase (alpha2,6-ST) or expression of its coding gene ST6GALNAC2 in peripheral B lymphocytes. Sixty patients with IgAN and 20 healthy controls were enrolled. Peripheral B lymphocytes were isolated by CD-19-positive magnetic beads. The expression level of ST6GALNAC2 was quantitatively analysed by real-time reverse-transcriptase polymerase chain reaction (PCR). Serum IgA1 and sialylation levels were detected by enzyme-linked immunosorbent assay (ELISA) and specific lectin-binding ELISA. Activity of alpha2,6-ST was measured by specific lectin-binding ELISA. Expression of ST6GALNAC2 in B peripheral lymphocytes was significantly lower in patients with IgAN than that in normal controls (3.7 +/- 2.2 versus 6.3 +/- 2.3, P = 0.016); alpha2,6-ST activity in B lymphocytes was correlated positively with the level of alpha2,6-sialic acid in serum IgA1 in patients (n = 42) and controls (n = 12) (r = 0.37, P = 0.007). However, alpha2,6-ST activity did not differ between patients with IgAN and controls (1.19 +/- 1.43 versus 1.06 +/- 1.17, P > 0.05). These data suggested that reduced sialylation of serum IgA1 may result from decreased expression of ST6GALNAC2. The factors affecting activity of alpha2,6-ST in the sialylation of IgA1 need to be further investigated.
 ...
PMID:Activity of alpha2,6-sialyltransferase and its gene expression in peripheral B lymphocytes in patients with IgA nephropathy. 1917 Sep 67