Growth Hormone Secretagogues and the Regulation of Calcium Signaling in Muscle

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Sep 8

PMID 31491959

Citations 4

Authors

Elena Bresciani

Laura Rizzi

Silvia Coco

Laura Molteni

Ramona Meanti

Vittorio Locatelli

Antonio Torsello

Affiliations

Soon will be listed here.

Abstract

Growth hormone secretagogues (GHS) are a family of synthetic molecules, first discovered in the late 1970s for their ability to stimulate growth hormone (GH) release. Many effects of GHS are mediated by binding to GHS-R1a, the receptor for the endogenous hormone ghrelin, a 28-amino acid peptide isolated from the stomach. Besides endocrine functions, both ghrelin and GHS are endowed with some relevant extraendocrine properties, including stimulation of food intake, anticonvulsant and anti-inflammatory effects, and protection of muscle tissue in different pathological conditions. In particular, ghrelin and GHS inhibit cardiomyocyte and endothelial cell apoptosis and improve cardiac left ventricular function during ischemia-reperfusion injury. Moreover, in a model of cisplatin-induced cachexia, GHS protect skeletal muscle from mitochondrial damage and improve lean mass recovery. Most of these effects are mediated by GHS ability to preserve intracellular Ca homeostasis. In this review, we address the muscle-specific protective effects of GHS mediated by Ca regulation, but also highlight recent findings of their therapeutic potential in pathological conditions characterized by skeletal or cardiac muscle impairment.

Citing Articles

Protective Effects of Hexarelin and JMV2894 in a Human Neuroblastoma Cell Line Expressing the SOD1-G93A Mutated Protein.

Meanti R, Licata M, Rizzi L, Bresciani E, Molteni L, Coco S Int J Mol Sci. 2023; 24(2).

PMID: 36674509 PMC: 9863688. DOI: 10.3390/ijms24020993.

Potential Applications for Growth Hormone Secretagogues Treatment of Amyotrophic Lateral Sclerosis.

Meanti R, Bresciani E, Rizzi L, Coco S, Zambelli V, Dimitroulas A Curr Neuropharmacol. 2022; 21(12):2376-2394.

PMID: 36111771 PMC: 10616926. DOI: 10.2174/1570159X20666220915103613.

Dynamic changes of miRNAs in skeletal muscle development at New Zealand rabbits.

Jing J, Jiang X, Zhu C, Zheng Q, Ji Q, Yin H BMC Genomics. 2021; 22(1):577.

PMID: 34315409 PMC: 8314457. DOI: 10.1186/s12864-021-07896-5.

Hexarelin Modulation of MAPK and PI3K/Akt Pathways in Neuro-2A Cells Inhibits Hydrogen Peroxide-Induced Apoptotic Toxicity.

Meanti R, Rizzi L, Bresciani E, Molteni L, Locatelli V, Coco S Pharmaceuticals (Basel). 2021; 14(5).

PMID: 34066741 PMC: 8150489. DOI: 10.3390/ph14050444.

References

Berti F, Muller E, De Gennaro Colonna V, Rossoni G . Hexarelin exhibits protective activity against cardiac ischaemia in hearts from growth hormone-deficient rats. Growth Horm IGF Res. 2000; 8 Suppl B:149-52. DOI: 10.1016/s1096-6374(98)80041-5. View

Mantovani G, Madeddu C . Cancer cachexia: medical management. Support Care Cancer. 2009; 18(1):1-9. DOI: 10.1007/s00520-009-0722-3. View

Bisi G, Podio V, Valetto M, Broglio F, Bertuccio G, Del Rio G . Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans. J Endocrinol Invest. 1999; 22(4):266-72. DOI: 10.1007/BF03343555. View

Imazio M, Bobbio M, Broglio F, Benso A, Podio V, Valetto M . GH-independent cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to dilated and ischemic cardiomyopathy. Eur J Heart Fail. 2002; 4(2):185-91. DOI: 10.1016/s1388-9842(01)00223-9. View

Moulin A, Demange L, Berge G, Gagne D, Ryan J, Mousseaux D . Toward potent ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure. 2. Synthesis and pharmacological in vitro and in vivo evaluations. J Med Chem. 2007; 50(23):5790-806. DOI: 10.1021/jm0704550. View

Virdis A, Lerman L, Regoli F, Ghiadoni L, Lerman A, Taddei S . Human Ghrelin: A Gastric Hormone with Cardiovascular Properties. Curr Pharm Des. 2015; 22(1):52-8. DOI: 10.2174/1381612822666151119144458. View

Missiaen L, Robberecht W, Van Den Bosch L, Callewaert G, Parys J, Wuytack F . Abnormal intracellular ca(2+)homeostasis and disease. Cell Calcium. 2000; 28(1):1-21. DOI: 10.1054/ceca.2000.0131. View

Alamri B, Shin K, Chappe V, Anini Y . The role of ghrelin in the regulation of glucose homeostasis. Horm Mol Biol Clin Investig. 2016; 26(1):3-11. DOI: 10.1515/hmbci-2016-0018. View

Pang J, Xu R, Xu X, Cao J, Ni C, Zhu W . Hexarelin protects rat cardiomyocytes from angiotensin II-induced apoptosis in vitro. Am J Physiol Heart Circ Physiol. 2003; 286(3):H1063-9. DOI: 10.1152/ajpheart.00648.2003. View

10.

Andersson D, Betzenhauser M, Reiken S, Meli A, Umanskaya A, Xie W . Ryanodine receptor oxidation causes intracellular calcium leak and muscle weakness in aging. Cell Metab. 2011; 14(2):196-207. PMC: 3690519. DOI: 10.1016/j.cmet.2011.05.014. View

11.

Fontes-Oliveira C, Busquets S, Toledo M, Penna F, Aylwin M, Sirisi S . Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia: altered energetic efficiency?. Biochim Biophys Acta. 2012; 1830(3):2770-8. DOI: 10.1016/j.bbagen.2012.11.009. View

12.

Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K . Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999; 402(6762):656-60. DOI: 10.1038/45230. View

13.

Broglio F, Guarracino F, Benso A, Gottero C, Prodam F, Granata R . Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery. Eur J Pharmacol. 2002; 448(2-3):193-200. DOI: 10.1016/s0014-2999(02)01934-9. View

14.

Delhanty P, Neggers S, van der Lely A . Should we consider des-acyl ghrelin as a separate hormone and if so, what does it do?. Front Horm Res. 2014; 42:163-74. DOI: 10.1159/000358345. View

15.

Demange L, Boeglin D, Moulin A, Mousseaux D, Ryan J, Berge G . Synthesis and pharmacological in vitro and in vivo evaluations of novel triazole derivatives as ligands of the ghrelin receptor. 1. J Med Chem. 2007; 50(8):1939-57. DOI: 10.1021/jm070024h. View

16.

Torsello A, Bresciani E, Rossoni G, Avallone R, Tulipano G, Cocchi D . Ghrelin plays a minor role in the physiological control of cardiac function in the rat. Endocrinology. 2003; 144(5):1787-92. DOI: 10.1210/en.2002-221048. View

17.

Ruiz-Garcia V, Lopez-Briz E, Carbonell-Sanchis R, Bort-Marti S, Gonzalvez-Perales J . Megestrol acetate for cachexia-anorexia syndrome. A systematic review. J Cachexia Sarcopenia Muscle. 2018; 9(3):444-452. PMC: 5989756. DOI: 10.1002/jcsm.12292. View

18.

Mosa R, Zhang Z, Shao R, Deng C, Chen J, Chen C . Implications of ghrelin and hexarelin in diabetes and diabetes-associated heart diseases. Endocrine. 2015; 49(2):307-23. DOI: 10.1007/s12020-015-0531-z. View

19.

Bellinger A, Reiken S, Dura M, Murphy P, Deng S, Landry D . Remodeling of ryanodine receptor complex causes "leaky" channels: a molecular mechanism for decreased exercise capacity. Proc Natl Acad Sci U S A. 2008; 105(6):2198-202. PMC: 2538898. DOI: 10.1073/pnas.0711074105. View

20.

Sakuma K, Aoi W, Yamaguchi A . Molecular mechanism of sarcopenia and cachexia: recent research advances. Pflugers Arch. 2017; 469(5-6):573-591. DOI: 10.1007/s00424-016-1933-3. View