| Literature DB >> 28011710 |
Beben Benyamin1,2, Adam X Maihofer3, Andrew J Schork4, Bruce A Hamilton5, Fangwen Rao5, Geert W Schmid-Schönbein6, Kuixing Zhang5, Manjula Mahata5, Mats Stridsberg7,8, Nicholas J Schork9, Nilima Biswas5, Vivian Y Hook5, Zhiyun Wei5, Grant W Montgomery2, Nicholas G Martin2, Caroline M Nievergelt3, John B Whitfield2, Daniel T O'Connor5.
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.Entities:
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Year: 2017 PMID： 28011710 PMCID： PMC6075630 DOI： 10.1093/hmg/ddw380
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150