Seung Hyun Yoo

Bio: Seung Hyun Yoo is an academic researcher from United States Department of Veterans Affairs. The author has contributed to research in topics: Chromogranin A & Nicotinic agonist. The author has an hindex of 2, co-authored 2 publications receiving 363 citations.

Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist.

Abstract: Catecholamine secretory vesicle core proteins (chromogranins) contain an activity that inhibits catecholamine release, but the identity of the responsible peptide has been elusive. Size-fractionated chromogranins antagonized nicotinic cholinergic-stimulated catecholamine secretion; the inhibitor was enriched in processed chromogranin fragments, and was liberated from purified chromogranin A. Of 15 synthetic peptides spanning approximately 80% of chromogranin A, one (bovine chromogranin A344-364 [RSMRLSFRARGYGFRGPGLQL], or catestatin) was a potent, dose-dependent (IC50 approximately 200 nM), reversible secretory inhibitor on pheochromocytoma and adrenal chromaffin cells, as well as noradrenergic neurites. An antibody directed against this peptide blocked the inhibitory effect of chromogranin A proteolytic fragments on nicotinic-stimulated catecholamine secretion. This region of chromogranin A is extensively processed within chromaffin vesicles in vivo. The inhibitory effect was specific for nicotinic cholinergic stimulation of catecholamine release, and was shared by this chromogranin A region from several species. Nicotinic cationic (Na+, Ca2+) signal transduction was specifically disrupted by catestatin. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. This small domain within chromogranin A may contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release from chromaffin cells and neurons.

A novel, catecholamine release-inhibitory peptide from chromogranin A: autocrine control of nicotinic cholinergic-stimulated exocytosis.

Abstract: Publisher Summary Proteolysis of chromogranin A takes place both within secretory granules and extracellularly, giving rise to several smaller, biologically active peptides, such as pancreastatin, which inhibits insulin and parathyroid hormone release, β-granin or vasostatin, which inhibits parathyroid hormone release and relaxes vascular smooth muscle, and parastatin which inhibits parathyroid hormone release. In search of the specific secretion-inhibitory domain within chromogranin A, 15 peptides (range, 19-25 residues) spanning 336 amino acids, or 78% of the length (431 amino acids) of the bovine chromogranin A mature protein were synthesized, and tested their efficacy on nicotine-induced norepinephrine secretion from rat pheochromocytoma (PC12) cells, screening each peptide at a 10-μM concentration. This chapter highlights that exposure of PC12 cells to a spectrum of nicotine doses (10-1000 μM), alone or with catestatin (10 μM), revealed that nicotine never overcame catestatin's inhibition of norepinephrine release, even at the highest nicotine dosage. Thus, catestatin is likely to be a noncompetitive nicotinic cholinergic antagonist. To explore the minimal catestatin domain exerting catecholamine secretion-inhibitory effect, we synthesized several (N-terminal, C-terminal, and bidirectional) truncated catestatin peptides. Catecholamine-release inhibitory mapped toward the N-terminus of catestatin, in a region of 12 or fewer amino acids.

The Chromogranin–Secretogranin Family

Abstract: The members of the chromogranin–secretogranin family of peptide hormones, biogenic amines, and neurotransmitters are enclosed within vesicles in the neuroendocrine system and a variety of neurons. These granins, the chief of which is chromogranin A, participate in sympathoadrenal activity and serve as markers of neuroendocrine tumors, especially pheochromocytoma.

Hypertension from targeted ablation of chromogranin A can be rescued by the human ortholog

Abstract: The secretory prohormone chromogranin A (CHGA) is overexpressed in essential hypertension, a complex trait with genetic predisposition, while its catecholamine release–inhibitory fragment catestatin is diminished, and low catestatin predicts augmented adrenergic pressor responses. These findings from studies on humans suggest a mechanism whereby diminished catestatin might increase the risk for hypertension. We generated Chga–/– and humanized mice through transgenic insertion of a human CHGA haplotype in order to probe CHGA and catestatin in vivo. Chga–/– mice displayed extreme phenotypic changes, including: (a) decreased chromaffin granule size and number; (b) elevated BP; (c) loss of diurnal BP variation; (d) increased left ventricular mass and cavity dimensions; (e) decreased adrenal catecholamine, neuropeptide Y (Npy), and ATP contents; (f) increased catecholamine/ATP ratio in the chromaffin granule; and (g) increased plasma catecholamine and Npy levels. Rescue of elevated BP to normalcy was achieved by either exogenous catestatin replacement or humanization of Chga–/– mice. Loss of the physiological “brake” catestatin in Chga–/– mice coupled with dysregulation of transmitter storage and release may act in concert to alter autonomic control of the circulation in vivo, eventuating in hypertension.

The Extended Granin Family: Structure, Function, and Biomedical Implications

Abstract: The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers.

Antimicrobial peptides: natural effectors of the innate immune system.

Abstract: Antimicrobial peptides (AMPs) are an evolutionarily conserved component of the innate immune system that defend against invading bacteria, viruses, and fungi through membrane or metabolic disruption. The efficiency of host defense via AMPs derives from the ability of these peptides to quickly identify and eradicate foreign pathogens through precise biochemical mechanisms. Recent advances in this field have expanded the repertoire of activities for AMPs to include immunostimulatory and immunomodulatory capacity as a catalyst for secondary host defense mechanisms. Further scrutiny of the biochemical and regulatory mechanisms of AMPs will lead to novel alternative approaches to the treatment of human pathogenic disorders.

The endocrine role for chromogranin A: a prohormone for peptides with regulatory properties.

Abstract: Chromogranin A (CgA) belongs to the granin family of uniquely acidic secretory proteins co-stored and co-secreted with other hormones and peptides in elements of the diffuse neuroendocrine system. The granins arise from different genes and are characterized by numerous sites for post-translational cleavage into shorter peptides with postulated regulatory properties. This review is directed towards endocrine aspects of CgA and its biologically active peptides. There is ample evidence from in vitro studies of distinct effects and targets for three CgA-derived peptides, vasostatin-I, pancreastatin and catestatin. Endocrine regulations are indicated from in vivo studies, consistent with the postulated prohormone function of CgA for peptides with regulatory properties. Most of the effects fit into patterns of direct or indirect, inhibitory modulations of major functions, implicating CgA peptides in regulation of calcium and glucose metabolism, cardiovascular functions, gastrointestinal motility and nociception, tissue repair, inflammatory responses and as host defense peptides in the first phase of microbial invasions.