THE NEURONAL ANTIINFLAMMATORY EFFECTS OF APELIN-13

Yıl 2023, Cilt: 6 Sayı: 2, 97 - 102, 31.08.2023

Akif Doğantekin , Esin Doğantekin , Nevzat Gözel

https://doi.org/10.56150/tjhsl.1241258

Cited By: 1

Öz

Objective: Apelin, a peptide with growth factor characteristic, is expressed in many cells and acts by binding to the APJ receptor. Apelin mRNA was detected in the central nervous system (CNS), macrophages and many peripheral tissues. According to recent studies, apelin protects neurons from hypoxia and glutamate-mediated excitotoxicity and can protect cells from oxidative stres (stress) (OS) damage by stimulating catalase activity. Pituitary and neurodegenerative diseases are associated with progressive neuronal loss in the CNS. Neuroinflammation and OS-induced cell damage, caused by microglia and astrocytes activation, have an important role in the pathogenesis and prognosis of these diseases. The aim of this study is to investigate the effects of apelin-13 molecule on the development of inflammation and OS caused by bacterial endotoxin in an invitro astrocyte cell culture medium. Methods: The effect of apelin -13 on cell viability changes in lipopolysaccharide (LPS) induced astrocyte inflammation was analyzed by enzymatic MTT test. The anti-inflammatory effects were determined by qRT-PCR and ELISA analysis at the level of TNF-α, IL-1β, IL-6 and mRNA transcription and protein. The effects of apelin on endotoxin mediated OS and possible DNA damage, lipid peroxidation, and nitric oxide (NO) production were evaluated by ELISA method. Results: In our study, LPS application to astrocytes caused inflammation and a significant decrease in inflammation was found with apelin treatment.
Conclusion: The results obtained from this study reveal the antiinflammatory, antiapoptotic and antioxidant effects of apelin, that have widely expressed receptors and role in the development of immune response on the development of neuroinflammation and oxidative cell damage.

Anahtar Kelimeler

Apelin, lipopolysaccharide, neuroinflammation, oxidative stres (stress)

Kaynakça

• Beltowski J. Apelin and visfatin: Unique "beneficial" adipokine supregulated in obesity? Medical Science Monitor 2006;; 12(6):112-119.
• Tatemoto K, Takayama K, Zou MX, Kumaki I, Zhang W, Kumano K, Fujimiya M. The novel peptide apelin lowers blood pressure via a nitric oxide-dependent mechanism. Regulatory Peptides 2001; 99(2-3): 87-92.
• Odowd BF, Heiber M, Chan A, Heng HHQ, Tsui LC, Kennedy JL, Shi XM, Petronis A, George SR, Nguyen TA. Human Gene That Shows Identity with the Gene Encoding the Angiotensin Receptor Is Located on Chromosome-11. Gene1993; 136(1-2): 355-360.
• Dickson DW. Apoptotic mechanisms in Alzheimer neurofibrillary degeneration: cause or effect? J Clin Invest2004; 114:23-27.
• Wee YV. ‘Inflammation in neurological disorders: a help or a hindrance?’ Neuroscientist 2010;16(4), 408-420.
• F. J. Mueller, S. R. McKercher, J. Imitola et al, 2005., ‘At the interface of the immune system and the nervous system: how neuroinflammation modulates the fate of neural progenitors in vivo.’ Ernst Schering Research Foundation workshop., no. 53, pp. 83-114.
• Ransohoffand RM, Brownn MA. ‘Innate immunity in the central nervous system’ Journal of Clinical Investigation 2012; 122: 1164-1171.
• Cheeseman KH, Slater TF, 1993; An introduction to free radical biochemistry. BritishMed Bulletin ;49:481-93.
• Kojima Y, Kundu R, Leeper N, Chun H. Apelin modulates adipocyte and inflammatory cell processes to inhibit atherosclerosis. American Heart Association 2009; 120:1064.
• Yenari MA, Kauppinen TM, Swanson RA. Microglial activation in stroke: therapeutic targets. Neurotherapeutics 2010; 7: 378-391.
• Obara S, Akifusa S, Ariyoshi W, Okinaga T, Usui M, Nakashima K, NishiraraT. Pyroglutamated Apelin-13 Inhibits Lipopolysaccharide-Induced Production of Pro-Inflammatory Cytokines in Murine Macrophage J774.1 Cells. Modern Research in Inflammation 2014;3:59-66.
• Xin Q, Cheng B , Pan Y, Liu H, Chunqing Y, Chen J, Bai B. Neuroprotective effects of apelin-13 on experimental ischemic stroke through suppression of inflammation. Peptides 2015;63:55-62.
• Kim H, Cheon B, Kim Y, Kim S. Effects of Naturally Occurring Flavonoids on Nitric Oxide Production in the Macrophage Cell Line RAW 264.7 and Their Structure–Activity Relationships. Biochemical Pharmacology1999; 58:759–765.
• Go HS, Shin CY, Lee S, Jeon S, Kim K, Choi C, Ko K. Increased Proliferation and Gliogenesis of Cultured Rat Neural Progenitor Cells by Lipopolysaccharide-Stimulated Astrocytes. Neuroimmunomodulation 2009;16:365–376.
• Zou Y, Wang B, Fu W, Zhou S, Nie Y, Tian S. Apelin-13 Protects PC12 Cells from Corticosterone-Induced Apoptosis Through PI3K and ERKs Activation. Neurochem Res 2016 Jul;41(7):1635-44. doi: 10.1007/s11064-016-1878-0. Epub 2016 Mar 9.
• Aktas O, Smorodchenko A, Brocke S, Infante-Duarte C, Schulze Topphoff U, Vogt J et al. Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL. Neuron. 2005 May 5;46(3):421-32.
• Yuan L, Wu Y, Ren X, Liu Q, Wang J, Liu X. Isoorientin attenuates lipopolysaccharide-induced pro-inflammatory responses through down-regulation of ROS-related MAPK/NF-κB signaling pathway in BV-2 microglia. Mol Cell Biochem. 2014 Jan;386(1-2):153-65. doi: 10.1007/s11010-013-1854-9. Epub 2013 Oct 11.
• Tuon T, Souza P, Santos M, Pereira F, Pedroso G, Luciano T, Souza C, Dutra R. Physical Training Regulates Mitochondrial Parameters and Neuroinflammatory Mechanisms in an Experimental Model of Parkinson’s Disease. Oxidative Medicine and Cellular Longevity 2015; Article ID 261809, 10 pages http://dx.doi.org/10.1155/2015/261809.
• Bienvenu J. Exploration of cytokines in biological fluids. CR Seances Soc Biol Fil 1993;189:545-555.
• Foussal C, Olivier L, Denis C, Pathak A. Activation of catalase by apelin prevents oxidative stress-linked cardiac hypertrophy, J Mol Neurosci 2010; 584:2363-2370.