Mouse Anti-Human Chromogranin A monoclonal antibody, clone JID655

Chromogranin A (CHGA) plays a fundamental role in the biogenesis of catecholamine secretory granules. Changes in storage and release of CHGA in clinical and experimental hypertension prompted us to study whether genetic variation at the CHGA locus might contribute to alterations in autonomic function, and hence hypertension and its target organ consequences such as hypertensive renal disease (nephrosclerosis). Systematic polymorphism discovery across the human CHGA locus revealed both common and unusual variants in both the open reading frame and such regulatory regions as the proximal promoter and 3'-UTR. In chromaffin cell-transfected CHGA 3'-UTR and promoter/luciferase reporter plasmids, the functional consequences of the regulatory/non-coding allelic variants were documented. Variants in both the proximal promoter and the 3'-UTR displayed statistical associations with hypertension. Genetic variation in the proximal CHGA promoter predicted glomerular filtration rate in healthy twins. However, for hypertensive renal damage, both end-stage renal disease and rate of progression of earlier disease were best predicted by variants in the 3'-UTR. Finally, mechanistic studies were undertaken initiated by the clue that CHGA promoter variation predicted circulating endothelin-1. In cultured endothelial cells, CHGA triggered co-release of not only the vasoconstrictor and pro-fibrotic endothelin-1, but also the pro-coagulant von Willebrand Factor and the pro-angiogenic angiopoietin-2. These findings, coupled with stimulation of endothelin-1 release from glomerular capillary endothelial cells by CHGA, suggest a plausible mechanism whereby genetic variation at the CHGA locus eventuates in alterations in human renal function. These results document the consequences of genetic variation at the CHGA locus for cardiorenal disease and suggest mechanisms whereby such variation achieves functional effects.

Composite chitosan membranes filled with various amount of iron ferroferric oxides (Fe3O4) cross-linked by two different agents, i.e. sulphuric acid (CHSA) and glutaraldehyde (CHGA) were prepared, and the pervaporation of water/ethanol mixture was investigated. The influence of cross-linking agents and iron oxide powder content on the transport properties were discussed. Permeation of water after addition of iron oxide nanoparticles to the polymer matrix for both types of cross-linking agents gradually increased. Furthermore, it was observed that the difference between permeation coefficients for ethanol and water was larger for membranes cross-linked by glutaraldehyde then for membranes cross-linked by sulphuric acid. Maximal evaluated the separation factor for CHGA membranes was about 2.5 times larger than for CHSA, and selectivity coefficient was 3.5 times larger. (C) 2014 Elsevier B.V. All rights reserved.