1.Ghrelin ameliorates the human alveolar epithelial A549 cell apoptosis induced by lipopolysaccharide.
Huang C1, Zheng H1, He W1, Lu G1, Li X1, Deng Y2, Zeng M3. Biochem Biophys Res Commun. 2016 May 20;474(1):83-90. doi: 10.1016/j.bbrc.2016.04.074. Epub 2016 Apr 19.
Ghrelin is a gastric acyl-peptide that plays an inhibitory role in cell apoptosis. Herein we investigate the protective effects of ghrelin in LPS-induced apoptosis of human alveolar epithelial A549 cells, along with the possible molecular mechanisms. LPS exposure impaired cell viability and increased apoptosis of A549 cells significantly in concentration- and time-dependent manners embodied in increased Bax and cleaved caspase-3 production, coupled with decreased Bcl-2 levels. Simultaneously, LPS remarkably decreased the expression of phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinas (ERK) in A549 cells. However, ghrelin'pretreatment ameliorated LPS-caused alterations in the ratio of Bax/Bcl-2 and cleaved caspase-3 expression, whereas activated the PI3K/Akt and ERK signaling. These results demonstrate that ghrelin lightens LPS-induced apoptosis of human alveolar epithelial cells partly through activating the PI3K/Akt and ERK pathway and thereby might benefit alleviating septic ALI.
2.Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZP-531, a First-in-class Analogue of Unacylated Ghrelin (UAG), in Healthy, Overweight/Obese, and Type 2 Diabetes Subjects.
Allas S1, Delale T1, Ngo N2, Julien M1, Sahakian P1, Ritter J3, Abribat T1, van der Lely AJ4. Diabetes Obes Metab. 2016 Apr 10. doi: 10.1111/dom.12675. [Epub ahead of print]
AIMS: To explore the safety, pharmacokinetics and pharmacodynamics in humans of the unacylated ghrelin analogue AZP-531 designed to improve glycemic control and reduce weight.
3.Intracoronary des-acyl ghrelin acutely increases cardiac perfusion through a nitric oxide-related mechanism in female anesthetized pigs.
Grossini E1, Raina G1, Farruggio S1, Camillo L1, Molinari C1, Mary D1, Elisabeth Walker G2, Bona G2, Vacca G1, Moia S2, Prodam F2, Surico D1. Endocrinology. 2016 Apr 21:en20151922. [Epub ahead of print]
Des-acyl ghrelin (DAG), the most abundant form of ghrelin in humans, has been found to reduce arterial blood pressure and prevent cardiac and endothelial cell apoptosis. Despite this, data regarding its direct effect on cardiac function and coronary blood flow, as well as the related involvement of autonomic nervous system and nitric oxide (NO), are scarce. We therefore examined these issues using both in vivo and in vitro studies. In 20 anesthetized pigs, intracoronary 100 pmol/ml DAG infusion with a constant heart rate and aortic blood pressure, increased coronary blood flow and NO release, whilst reducing coronary vascular resistances (P<0.05). Dose-responses to DAG were evaluated in 5 pigs. No effects on cardiac contractility/relaxation or myocardial oxygen consumption were observed. Moreover, while the blockade of muscarinic cholinoceptors (n = 5) or α and β-adrenoceptors (n = 5 each) did not abolish the observed responses, NO synthase inhibition (n = 5) prevented the effects of DAG on CBF and NO release.
4.Mole ghrelin: cDNA cloning, gene expression, and diverse molecular forms in Mogera imaizumii.
Satou M1, Kaiya H2, Nishi Y3, Shinohara A4, Kawada SI5, Miyazato M2, Kangawa K2, Sugimoto H6. Gen Comp Endocrinol. 2016 Apr 18. pii: S0016-6480(16)30091-0. doi: 10.1016/j.ygcen.2016.04.014. [Epub ahead of print]
Here, we describe cDNA cloning and purification of the ghrelin gene sequences and ghrelin peptides from the Japanese true mole, Mogera imaizumii. The gene spans > 2.9 kbp, has four exons and three introns, and shares structural similarity with those of terrestrial animals. Mature mole ghrelin peptide was predicted to be 28 amino acids long (GSSFLSPEHQKVQQRKESKKPPSKPQPR) and processed from a prepropeptide of 116 amino acids. To further elucidate molecular characteristics, we purified ghrelin peptides from mole stomach. By mass spectrometry, we found that the mole ghrelin peptides had higher ratios of the odd-number fatty acids (C9 and C11 as much as C8) attached to the third serine residue than other vertebrate ghrelin. Truncated forms of ghrelins such as [1-27], [1-19], [1-16] and [1-15], and that lacked the 14th glutamine residue (des-Gln14 ghrelin) were produced in the stomach. Marked expression of ghrelin mRNA in lung was observed as in stomach and brain.
