| 1. |
- Benyamin, Beben, et al.
(författare)
-
Identification of novel loci affecting circulating chromogranins and related peptides
- 2017
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 26:1, s. 233-242
-
Tidskriftsartikel (refereegranskat)abstract
- Chromogranins are pro-hormone secretory proteins released from neuroendocrine cells, with effects on control of blood pressure. We conducted a genome-wide association study for plasma catestatin, the catecholamine release inhibitory peptide derived from chromogranin A (CHGA), and other CHGA- or chromogranin B (CHGB)-related peptides, in 545 US and 1252 Australian subjects. This identified loci on chromosomes 4q35 and 5q34 affecting catestatin concentration (P = 3.40 × 10(-30) for rs4253311 and 1.85 × 10(-19) for rs2731672, respectively). Genes in these regions include the proteolytic enzymes kallikrein (KLKB1) and Factor XII (F12). In chromaffin cells, CHGA and KLKB1 proteins co-localized in catecholamine storage granules. In vitro, kallikrein cleaved recombinant human CHGA to catestatin, verified by mass spectrometry. The peptide identified from this digestion (CHGA360-373) selectively inhibited nicotinic cholinergic stimulated catecholamine release from chromaffin cells. A proteolytic cascade involving kallikrein and Factor XII cleaves chromogranins to active compounds both in vivo and in vitro.
|
|
| 2. |
- Chen, Wei, et al.
(författare)
-
Highly sensitive detection of low-level water content in organic solvents and cyanide in aqueous media using novel solvatochromic AIEE fluorophores
- 2015
-
Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 5:16, s. 12191-12201
-
Tidskriftsartikel (refereegranskat)abstract
- A great deal of effort has been devoted to develop easy-to-use fluorescent probes for detecting analytes due to their advantages in the field of chemo- and bio-sensing. Herein, two novel 2,2 '-biindenyl-based derivatives BDM and BDBM containing dicyanovinyl groups have been designed and synthesized, and are shown to possess the remarkable dual properties of solvatochromism and aggregation-induced emission enhancement (AIEE). Importantly, both of them are found to serve as fluorescent indicators for the qualitative and quantitative detection of low-level water in organic solvents. Meanwhile, both BDM and BDBM emit yellowish orange and orange fluorescence, respectively, in their aggregated states. Furthermore, with dicyanovinyl groups as the recognition sites, both compounds can act as colourimetric and fluorescent sensors for highly sensitive and selective detection of cyanide in aqueous media, and the apparent response signals can be observed by the naked eye even in the presence of various interference anions, promising practical applications for detecting cyanide in drinking water. Besides, optical spectroscopic techniques, NMR titration measurements, and density functional theory calculations are conducted to rationalize the sensing mechanisms of the two probes.
|
|
| 3. |
- Hightower, C. Makena, et al.
(författare)
-
Genetic variation at the delta-sarcoglycan (SGCD) locus elevates heritable sympathetic nerve activity in human twin pairs
- 2013
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 127:6, s. 750-761
-
Tidskriftsartikel (refereegranskat)abstract
- The Syrian Cardiomyopathic Hamster (BIO-14.6/53.58 strains) model of cardiac failure, resulting from naturally occurring deletion at the SGCD (delta-sarcoglycan) locus, displays widespread disturbances in catecholamine metabolism. Rare Mendelian myopathy disorders of human SGCD occur, although common naturally occurring SGCD genetic variation has not been evaluated for effects on human norepinephrine (NE) secretion. This study investigated the effect of SGCD genetic variation on control of NE secretion in healthy twin pairs. Genetic associations profiled SNPs across the SGCD locus. Trait heritability (h(2)) and genetic covariance (pleiotropy; shared h(2)) were evaluated. Sympathochromaffin exocytosis in vivo was probed in plasma by both catecholamines and Chromogranin B (CHGB). Plasma NE is substantially heritable (p=3.19E-16, at 65.2 +/- 5.0% of trait variance), sharing significant (p<0.05) genetic determination with circulating and urinary catecholamines, CHGB, eGFR, and several cardio-metabolic traits. Participants with higher pNE showed significant (p<0.05) differences in several traits, including increased BP and hypertension risk factors. Peak SGCD variant rs1835919 predicted elevated systemic vascular compliance, without changes in specifically myocardial traits. We used a chimeric-regulated secretory pathway photoprotein (CHGA-EAP) to evaluate the effect of SGCD on the exocytotic pathway in transfected PC12 cells; in transfected cells, expression of SGCD augmented CHGA trafficking into the exocytotic regulated secretory pathway. Thus, our investigation determined human NE secretion to be a highly heritable trait, influenced by common genetic variation within the SGCD locus. Circulating NE aggregates with BP and hypertension risk factors. In addition, coordinate NE and CHGB elevation by rs1835919 implicates exocytosis as the mechanism of release.
|
|
