Antioxidant properties of a human neuropeptide and its protective effect on free radical‐induced DNA damage

Abstract

Human catestatin CgA352-372 (SL21) is an endogenous neuropeptide with multiple biological functions. The present study aimed to evaluate the antioxidant, antibacterial, cytotoxic, and DNA damage protective effects of SL21 neuropeptide. SL21 neuropeptide generated from the C-terminus of chromogranin A (CgA) was synthesized by solid-phase method. Synthetic peptide was subjected to various in vitro antioxidant assays including the scavenging of 1,1-diphenyl-2-pycryl-hydrazyl (DPPH), 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(·+) ), and hydroxyl free radicals, metal ion chelation, inhibition of lipid peroxidation, and reducing power. Moreover, protective effect of SL21 on H2 O2 -induced DNA damage was analyzed using pTZ57/RT plasmid. Methylthiazoltetrazolium assay was also performed to study the cytotoxic effect of SL21 neuropeptide on human peripheral blood mononuclear cells. Furthermore, antibacterial and hemolysis assays were conducted. The results demonstrated high activities of SL21 in scavenging free radicals (DPPH, ABTS(·+) , and hydroxyl), chelating of Cu(2+) /Fe(2+) metal ions, reducing power, and inhibition of lipid peroxidation in a concentration-dependent manner. SL21 neuropeptide revealed a protective effect on DNA damage caused by hydroxyl radicals. Interestingly, the peptide exhibited no significant cytotoxicity towards peripheral blood mononuclear cells. Furthermore, SL21 peptide displayed antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa without any hemolytic activity on human red blood cells. Conclusively, the present study established SL21 (catestatin) as a novel antioxidative peptide that could further be investigated for its potential use as a pharmaceutical agent.

Chromogranina A i jej rola w patogenezie cukrzycy

“…It can be assumed that the C-terminus of WE-14 can interact with the MHC class II I-A g7 at a site outside of the normal peptide binding groove [11]. Outside Decreased plasma concentration in essential hypertension [165] Counter-regulation of the β-adrenergic and endothelin-1 stimulated action [166] and antiadrenergic effect [167] Normalisation of baroreflex [132] Improved insulin sensitivity in catestatin-knockout mice [133] Induction of angiogenesis [168] Antimicrobial activity against bacteria, fungi, and yeasts [164] Antioxidant activity [169] Effective catecholamine release inhibition and endogenous nicotinic cholinergic antagonistic effect [113,132] Obesity-reducing effects [131] X CgA 357-428 Porcine Parastatin Inhibition of the low Ca 2+ -stimulated parathyroid secretion in vitro [170,171] CgA of pancreatic β-cells in NOD mice, the CgA-induced CD4 + autoimmune reactions of other gastro-enteropancreatic tissues were not supported [42]. The observation that the CgA-induced autoimmune reaction is only detectable in the beta cells is still unclear to our present knowledge, although several theories have been proposed [11]: 1.…”

DFT study on addition reaction mechanism of guanine-cytosine base pair with OH radical

“…Most of the effects have belonged to the role of free radicals . It is known that free radicals constantly formed in living organisms by x‐rays, radiation therapy, and ultraviolet radiations could react with organic cellular components, such as protein, lipid, and nucleic acid . Especially, OH radical, as a highly reactive oxygen species, has an extremely short lifetime and plays a vital character for DNA damage .…”

Plasma Catestatin Levels and Advanced Glycation End Products in Patients on Hemodialysis

“…HD is associated with a low-grade chronic inflammation and oxidative stress which is due to loss of antioxidants and stimulation of leukocytes during dialysis which triggers production of reactive oxygen species (ROS) [42][43][44]. Several recent studies suggested that that protective role of CST is mediated by preventing DNA damage caused by ROS, reducing endoplasmic reticulum stress-induced apoptosis and scavenging free radicals [45][46][47][48], while the study conducted by Aung et al implied that CST also has an immunomodulatory function, as they determined that CST has a role in inflammation by causing mast cells to release leukotrienes, prostaglandins, cytokines and chemokines [49]. Another recent cohort study on patients with heart failure with reduced ejection fraction (HFrEF) showed that CST levels could predict all-cause and unplanned hospitalizations [50].…”