Catestatin

Increased plasma level of catestatin might be associated with poor prognosis in hemodialysis patients.[Pubmed:28161844]

Int Urol Nephrol. 2017 Jun;49(6):1063-1069.

PURPOSE: Cardiac complication is a major cause of death in hemodialysis patients. The aim of the study was to determine the relationship between plasma Catestatin level and cardiac death in those people. METHODS: A total of 330 maintenance hemodialysis patients were included. Blood samples were collected. Plasma Catestatin level was detected by enzyme-linked immunosorbent assay. Fluid status of each patient was expressed by overhydration to total body weight ratio and daily diuresis. Each patient was followed-up for 36 months, unless some of them died in the follow-up period. RESULTS: In the follow-up period, only one hemodialysis patient was lost, 29 patients were died of cardiovascular diseases, 28 patients were died of other diseases and remaining 272 patients survived. Logistic multivariate regression analysis revealed that patients with plasma Catestatin level >/=1.9 ng/ml were associated with increased cardiac death risk (RR 6.13, 95% CI 2.54, 18.45), and survival analysis also showed that cardiac death rate in patients with plasma Catestatin level >/=1.9 ng/ml was elevated than that in patients with plasma Catestatin level <1.9 ng/ml (P < 0.001). In addition, overhydration to total body weight ratio and daily diuresis both had significant linear correlations with plasma Catestatin level (r = 0.502, P < 0.001 and r = -0.338, P < 0.001). CONCLUSION: Circulating Catestatin concentration might be an independent cardiac prognostic indicator in hemodialysis patients. Fluid status might be involved in the prognostic forecasting process.

Human Catestatin Alters Gut Microbiota Composition in Mice.[Pubmed:28144234]

Front Microbiol. 2017 Jan 17;7:2151.

The mammalian intestinal tract is heavily colonized with a dense, complex, and diversified microbial populations. In healthy individuals, an array of epithelial antimicrobial agents is secreted in the gut to aid intestinal homeostasis. Enterochromaffin cells (EC) in the intestinal epithelium are a major source of chromogranin A (CgA), which is a pro-hormone and can be cleaved into many bioactive peptides that include Catestatin (CST). This study was carried out to evaluate the possible impact of CST on gut microbiota in vivo using a mouse model. The CST (Human CgA352-372) or normal saline was intrarectally administered in C57BL/6 male mice for 6 days and then sacrificed. Feces and colonic mucosa tissue samples were collected, DNA was extracted, the V4 region of bacterial 16S rRNA gene was amplified and subjected to MiSeq Illumina sequencing. The alpha-diversity was calculated using Chao 1 and beta-diversity was determined using QIIME. Differences at the genus level were determined using partial least square discriminant analysis (PLS-DA). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict functional capacity of bacterial community. CST treatment did not modify bacterial richness in fecal and colonic mucosa-associated microbiota; however, treatment significantly modified bacterial community composition between the groups. Also, CST-treated mice had a significantly lower relative abundance of Firmicutes and higher abundance of Bacteroidetes, observed only in fecal samples. However, at lower phylogenetic levels, PLS-DA analysis revealed that some bacterial taxa were significantly associated with the CST-treated mice in both fecal and colonic mucosa samples. In addition, differences in predicted microbial functional pathways in both fecal and colonic mucosa samples were detected. The results support the hypothesis that CST treatment modulates gut microbiota composition under non-pathophysiological conditions, however, the result of this study needs to be further validated in a larger experiment. The data may open new avenues for the development of a potential new line of antimicrobial peptides and their use as therapeutic agents to treat several inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), or other health conditions.

Catestatin, vasostatin, cortisol, and pain assessments in dogs suffering from traumatic bone fractures.[Pubmed:28327184]

BMC Res Notes. 2017 Mar 21;10(1):129.

BACKGROUND: Traumatic bone fractures cause moderate to severe pain, which needs to be minimized for optimal recovery and animal welfare, illustrating the need for reliable objective pain biomarkers for use in a clinical setting. The objectives of this study were to investigate Catestatin (CST) and vasostatin (VS) concentrations as two new potential biomarkers, and cortisol concentrations, scores of the short form of the Glasgow composite measure pain scale (CMPS-SF), and visual analog scale (VAS) in dogs suffering from traumatic bone fractures before and after morphine administration in comparison with healthy dogs. METHODS: Fourteen dogs with hind limb or pelvic fractures and thirty healthy dogs were included. Dogs with fractures were divided into four groups according to analgesia received before participation. Physical examination, CMPS-SF, pain and stress behavior VAS scores were recorded in all dogs. Saliva and blood were collected once in healthy dogs and in dogs with fractures before and 35-70 min after morphine administration. Blood samples were analyzed for CST, VS, and cortisol. Saliva volumes, however, were insufficient for analysis. RESULTS: Catestatin and cortisol concentrations, and CMPS-SF, and VAS scores differed significantly between dogs with fractures prior to morphine administration and healthy dogs. After morphine administration, dogs with fractures had significantly decreased CMPS-SF and VAS scores and, compared to healthy dogs, CST concentrations, CMPS-SF, and VAS scores still differed significantly. However, CST concentrations remained largely within the normal range. Absolute delta values for CST significantly correlated with delta values for CMPS-SF. Catestatin and cortisol did not differ significantly before and after morphine administration. Vasostatin concentrations did not differ significantly between groups. CONCLUSIONS: Catestatin and cortisol concentrations, CMPS-SF, and VAS scores differed significantly in the dogs with traumatic bone fractures compared to the healthy dogs. Morphine treatment partially relieved pain and stress according to the subjective but not according to the objective assessments performed. However, because of the large degree of overlap with normal values, our results suggest that plasma CST concentrations have a limited potential as a clinically useful biomarker for pain-induced stress.

Primary structure and function of the catecholamine release inhibitory peptide catestatin (chromogranin A(344-364)): identification of amino acid residues crucial for activity.[Pubmed:11043569]

Mol Endocrinol. 2000 Oct;14(10):1525-35.

The novel chromogranin A fragment Catestatin (bovine chromogranin A(344-364); RSMRLSFRARGYGFRGPGLQL) is a potent inhibitor of catecholamine release (IC50, approximately 0.2-0.3 microM) by acting as a nicotinic cholinergic antagonist. To define the minimal active region within Catestatin, we tested the potencies of synthetic serial three-residue deletion (amino-terminal, carboxyl-terminal, or bidirectional) fragments to inhibit nicotine-stimulated catecholamine secretion from PC12 pheochromocytoma cells. The results revealed that a completely active core sequence of Catestatin was constituted by chromogranin A(344-364). Nicotinic cationic signal transduction was affected by Catestatin fragments in a manner similar to that for secretion (confirming the functional importance of the amino-terminus). To identify crucial residues within the active core, we tested serial single amino acid truncations or single residue substitutions by alanine on nicotine-induced catecholamine secretion and desensitization. Nicotinic inhibition by the active Catestatin core was diminished by even single amino acid deletions. Selective alanine substitution mutagenesis of the active core revealed important roles for Met346, Leu348, Phe350, Arg351, Arg353, Gly354, Tyr355, Phe357, and Arg358 on catecholamine secretion, whereas crucial roles to inhibit desensitization of catecholamine release were noted for Arg344, Met346, Leu348, Ser349, Phe350, Arg353, Gly354, Tyr355, Gly356, and Arg358. We conclude that a small, 15-amino acid core of Catestatin (chromogranin A(344-364)) is sufficient to exert the peptide's typical inhibitory effects on nicotinic cholinergic-stimulated catecholamine secretion, signal transduction, and desensitization. These studies refine the biologically active domains of Catestatin and suggest that the pharmacophores for inhibition of nicotinic secretion and desensitization may not be identical.

Novel autocrine feedback control of catecholamine release. A discrete chromogranin a fragment is a noncompetitive nicotinic cholinergic antagonist.[Pubmed:9294131]

J Clin Invest. 1997 Sep 15;100(6):1623-33.

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.