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Review Article

SGK-1 Signalling Pathway is a Key Factor in Cell Survival in Ischemic Injury

Author(s): Manisha Chaudhary, Veerta Sharma, Onkar Bedi, Amarjot Kaur and Thakur Gurjeet Singh*

Volume 24, Issue 14, 2023

Published on: 22 October, 2023

Page: [1117 - 1126] Pages: 10

DOI: 10.2174/0113894501239948231013072901

Price: $65

Abstract

Serum and glucocorticoid-regulated kinases (SGK) are serine/threonine kinases that belong to AGC. The SGK-1, which responds to stress, controls a range of ion channels, cell growth, transcription factors, membrane transporters, cellular enzymes, cell survival, proliferation and death. Its expression is highly controlled by various factors such as hyperosmotic or isotonic oxidative stress, cell shrinkage, radiation, high blood sugar, neuronal injury, DNA damage, mechanical stress, thermal shock, excitement, dehydration and ischemia. The structural and functional deterioration that arises after a period of ischemia when blood flow is restored is referred to as ischemia/ reperfusion injury (I/R). The current review discusses the structure, expression, function and degradation of SGK-1 with special emphasis on the various ischemic injuries in different organs such as renal, myocardial, cerebral, intestinal and lungs. Furthermore, this review highlights the various therapeutic agents that activate the SGK-1 pathway and slow down the progression of I/R injuries.

Keywords: SGK-1, inflammation, oxidative stress, Ischemia-reperfusion, apoptosis, cell survival.

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[1]
Lang F, Cohen P. Regulation and physiological roles of serum-and glucocorticoid-induced protein kinase isoforms. Sci STKE 2001; 2001(108): re17.
[http://dx.doi.org/10.1126/stke.2001.108.re17] [PMID: 11707620]
[2]
Lang F, Strutz-Seebohm N, Seebohm G, Lang UE. Significance of SGK1 in the regulation of neuronal function. J Physiol 2010; 588(18): 3349-54.
[http://dx.doi.org/10.1113/jphysiol.2010.190926] [PMID: 20530112]
[3]
Firestone G, Giampaolo J, O’Keeffe B. Stimulus-dependent regulation of serum and glucocorticoid inducible protein kinase (SGK) transcription, subcellular localization and enzymatic activity. Cell Physiol Biochem 2003; 13(1): 1-12.
[http://dx.doi.org/10.1159/000070244] [PMID: 12649597]
[4]
Lang F, Henke G, Embark H, et al. Regulation of channels by the serum and glucocorticoid-inducible kinase-implications for transport, excitability and cell proliferation. Cell Physiol Biochem 2003; 13(1): 41-50.
[http://dx.doi.org/10.1159/000070248] [PMID: 12649601]
[5]
Nishida Y, Nagata T, Takahashi Y, Sugahara-Kobayashi M, Murata A, Asai S. Alteration of serum/glucocorticoid regulated kinase-1 (sgk-1) gene expression in rat hippocampus after transient global ischemia. Brain Res Mol Brain Res 2004; 123(1-2): 121-5.
[http://dx.doi.org/10.1016/j.molbrainres.2004.01.008] [PMID: 15046873]
[6]
Behl T, Rana T, Sehgal A, et al. Phytochemicals targeting nitric oxide signaling in neurodegenerative diseases. Nitric Oxide 2022.
[PMID: 36375788]
[7]
Cowled P, Fitridge R. Pathophysiology of reperfusion injury. Mechanisms of Vascular Disease 2020; 415-0.
[http://dx.doi.org/10.1007/978-3-030-43683-4_18]
[8]
Heise CJ, Xu B, Deaton SL, et al. Serum and glucocorticoid-induced kinase (SGK) 1 and the epithelial sodium channel are regulated by multiple with no lysine (WNK) family members. J Biol Chem 2010; 285(33): 25161-7.
[http://dx.doi.org/10.1074/jbc.M110.103432] [PMID: 20525693]
[9]
Zhao B, Lehr R, Smallwood AM, et al. Crystal structure of the kinase domain of serum and glucocorticoid-regulated kinase 1 in complex with AMP-PNP. Protein Sci 2007; 16(12): 2761-9.
[http://dx.doi.org/10.1110/ps.073161707] [PMID: 17965184]
[10]
Akhoon BA, Gandhi NS, Pandey R. Computational insights into the active structure of SGK1 and its implication for ligand design. Biochimie 2019; 165: 57-66.
[http://dx.doi.org/10.1016/j.biochi.2019.07.007] [PMID: 31302161]
[11]
Vallon V, Schroth J, Lang F, Kuhl D, Uchida S. Expression and phosphorylation of the Na + -Cl − cotransporter NCC in vivo is regulated by dietary salt, potassium, and SGK1. Am J Physiol Renal Physiol 2009; 297(3): F704-12.
[http://dx.doi.org/10.1152/ajprenal.00030.2009] [PMID: 19570885]
[12]
Hong G, Lockhart A, Davis B, et al. PPARγ activation enhances cell surface ENaCα via up-regulation of SGK1 in human collecting duct cells. FASEB J 2003; 17(13): 1-17.
[http://dx.doi.org/10.1096/fj.03-0181fje] [PMID: 12923071]
[13]
Brunet A, Park J, Tran H, Hu LS, Hemmings BA, Greenberg ME. Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a). Mol Cell Biol 2001; 21(3): 952-65.
[http://dx.doi.org/10.1128/MCB.21.3.952-965.2001] [PMID: 11154281]
[14]
Anacker C, Cattaneo A, Musaelyan K, et al. Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis. Proc Natl Acad Sci USA 2013; 110(21): 8708-13.
[http://dx.doi.org/10.1073/pnas.1300886110] [PMID: 23650397]
[15]
Debonneville C, Flores SY, Kamynina E, et al. Phosphorylation of Nedd4-2 by Sgk1 regulates epithelial Na+ channel cell surface expression. EMBO J 2001; 20(24): 7052-9.
[http://dx.doi.org/10.1093/emboj/20.24.7052] [PMID: 11742982]
[16]
Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol 2012; 298: 229-317.
[http://dx.doi.org/10.1016/B978-0-12-394309-5.00006-7] [PMID: 22878108]
[17]
Huang M, Singh N, Kainth R, Khalid M, Kushwah AS, Kumar M. Mechanistic insight into diosmin-induced neuroprotection and memory improvement in intracerebroventricular-quinolinic acid rat model: Resurrection of mitochondrial functions and antioxidants. Evid Based Complement Alternat Med 2022; 2022: 1-14.
[http://dx.doi.org/10.1155/2022/8584558] [PMID: 35300069]
[18]
Pastore D, Della-Morte D, Coppola A, et al. SGK-1 protects kidney cells against apoptosis induced by ceramide and TNF-α. Cell Death Dis 2015; 6(9): e1890.
[http://dx.doi.org/10.1038/cddis.2015.232] [PMID: 26379195]
[19]
Rehni AK, Nautiyal N, Perez-Pinzon MA, Dave KR. Hyperglycemia / hypoglycemia-induced mitochondrial dysfunction and cerebral ischemic damage in diabetics. Metab Brain Dis 2015; 30(2): 437-47.
[http://dx.doi.org/10.1007/s11011-014-9538-z] [PMID: 24737446]
[20]
Rusai K, Prokai A, Juanxing C, et al. Dexamethasone protects from renal ischemia/reperfusion injury: A possible association with SGK-1. Acta Physiol Hung 2013; 100(2): 173-85.
[http://dx.doi.org/10.1556/APhysiol.100.2013.001] [PMID: 23524182]
[21]
Rusai K, Prókai Á, Szebeni B, et al. Role of serum and glucocorticoid-regulated kinase-1 in the protective effects of erythropoietin during renal ischemia/reperfusion injury. Biochem Pharmacol 2010; 79(8): 1173-81.
[http://dx.doi.org/10.1016/j.bcp.2009.11.022] [PMID: 19961832]
[22]
Kimura T, Takabatake Y, Takahashi A, et al. Autophagy protects the proximal tubule from degeneration and acute ischemic injury. J Am Soc Nephrol 2011; 22(5): 902-13.
[http://dx.doi.org/10.1681/ASN.2010070705] [PMID: 21493778]
[23]
Satake A, Takaoka M, Nishikawa M, et al. Protective effect of 17β-estradiol on ischemic acute renal failure through the PI3K/Akt/eNOS pathway. Kidney Int 2008; 73(3): 308-17.
[http://dx.doi.org/10.1038/sj.ki.5002690] [PMID: 18004295]
[24]
Lin M, Li L, Li L, et al. The protective effect of baicalin against renal ischemia-reperfusion injury through inhibition of inflammation and apoptosis. BMC Complement Altern Med 2014; 14(1): 19.
[http://dx.doi.org/10.1186/1472-6882-14-19] [PMID: 24417870]
[25]
Baban B, Liu JY, Mozaffari MS. SGK-1 regulates inflammation and cell death in the ischemic-reperfused heart: Pressure-related effects. Am J Hypertens 2014; 27(6): 846-56.
[http://dx.doi.org/10.1093/ajh/hpt269] [PMID: 24429675]
[26]
Calderón-Sánchez E, Díaz I, Ordóñez A, Smani T. Urocortin-1 mediated cardioprotection involves XIAP and CD40-ligand recovery: role of EPAC2 and ERK1/2. PLoS One 2016; 11(2): e0147375.
[http://dx.doi.org/10.1371/journal.pone.0147375] [PMID: 26840743]
[27]
Cong B, Wang L, Zhu X, Li X, Liu B, Ni X. SGK1 is involved in cardioprotection of urocortin-1 against hypoxia/reoxygenation in cardiomyocytes. Can J Cardiol 2014; 30(6): 687-95.
[http://dx.doi.org/10.1016/j.cjca.2014.03.024] [PMID: 24882544]
[28]
Cong B, Du J, Zhu X, Lu J, Ni X. Estrogen enhancement of SGK1 expression induced by urocortin contributes to its cardioprotection against ischemia/reperfusion insult. Int J Cardiol 2015; 178: 200-2.
[http://dx.doi.org/10.1016/j.ijcard.2014.10.113] [PMID: 25464253]
[29]
Jiang H, Xiao J, Kang B, Zhu X, Xin N, Wang Z. PI3K/SGK1/GSK3β signaling pathway is involved in inhibition of autophagy in neonatal rat cardiomyocytes exposed to hypoxia/reoxygenation by hydrogen sulfide. Exp Cell Res 2016; 345(2): 134-40.
[http://dx.doi.org/10.1016/j.yexcr.2015.07.005] [PMID: 26163895]
[30]
Yang Q, Huang DD, Li DG, et al. Tetramethylpyrazine exerts a protective effect against injury from acute myocardial ischemia by regulating the PI3K/Akt/GSK-3β signaling pathway. Cell Mol Biol Lett 2019; 24(1): 17.
[http://dx.doi.org/10.1186/s11658-019-0141-5]
[31]
McCaig C, Ataliotis P, Shtaya A, et al. Induction of the cell survival kinase Sgk1: A possible novel mechanism for α-phenyl-N-tert-butyl nitrone in experimental stroke. J Cereb Blood Flow Metab 2019; 39(6): 1111-21.
[http://dx.doi.org/10.1177/0271678X17746980] [PMID: 29260627]
[32]
Wang D, Huang Z, Li L, et al. Intracarotid cold saline infusion contributes to neuroprotection in MCAO-induced ischemic stroke in rats via serum and glucocorticoid-regulated kinase 1. Mol Med Rep 2019; 20(4): 3942-50.
[http://dx.doi.org/10.3892/mmr.2019.10599] [PMID: 31485662]
[33]
Zhang W, Qian C, Li S. Protective effect of SGK1 in rat hippocampal neurons subjected to ischemia reperfusion. Cell Physiol Biochem 2014; 34(2): 299-312.
[http://dx.doi.org/10.1159/000363000] [PMID: 25034177]
[34]
Yu C, Liu S, Liu J, Cao H, Liu X, Cai X. Effects of curcumin on injury in hippocampal neurons and expression of blood corticosterone and SGK1 in hippocampal during global cerebral ischemia-reperfusion injury in hypertensive rats. Chinese Journal of Clinical Pharmacology and Therapeutics 2019; 24(7): 737.
[35]
Chi OZ, Chiricolo A, Liu X, Patel N, Jacinto E, Weiss HR. Inhibition of serum and glucocorticoid regulated kinases by GSK650394 reduced infarct size in early cerebral ischemia-reperfusion with decreased BBB disruption. Neurosci Lett 2021; 762: 136143.
[http://dx.doi.org/10.1016/j.neulet.2021.136143] [PMID: 34332027]
[36]
Kuntzsch D, Bergann T, Dames P, et al. The plant-derived glucocorticoid receptor agonist Endiandrin A acts as co-stimulator of colonic epithelial sodium channels (ENaC) via SGK-1 and MAPKs. PLoS One 2012; 7(11): e49426.
[http://dx.doi.org/10.1371/journal.pone.0049426] [PMID: 23152905]
[37]
Kawasaki T, Chaudry IH. The effects of estrogen on various organs: therapeutic approach for sepsis, trauma, and reperfusion injury. Part 2: liver, intestine, spleen, and kidney. J Anesth 2012; 26(6): 892-9.
[http://dx.doi.org/10.1007/s00540-012-1426-2] [PMID: 22729228]
[38]
Dong Y, Lei J, Zhang B. Dietary quercetin alleviated DSS-induced colitis in mice through several possible pathways by transcriptome analysis. Curr Pharm Biotechnol 2020; 21(15): 1666-73.
[http://dx.doi.org/10.2174/1389201021666200711152726] [PMID: 32651963]
[39]
Wu CP, Huang KL, Peng CK, Lan CC. Acute hyperglycemia aggravates lung injury via activation of the SGK1–NKCC1 pathway. Int J Mol Sci 2020; 21(13): 4803.
[http://dx.doi.org/10.3390/ijms21134803] [PMID: 32645929]
[40]
Shen CH, Lin JY, Chang YL, et al. Inhibition of NKCC1 modulates alveolar fluid clearance and inflammation in ischemia-reperfusion lung injury via TRAF6-mediated pathways. Front Immunol 2018; 9: 2049.
[http://dx.doi.org/10.3389/fimmu.2018.02049] [PMID: 30271405]
[41]
Qi D, He J, Wang D, et al. 17β-estradiol suppresses lipopolysaccharide-induced acute lung injury through PI3K/Akt/SGK1 mediated up-regulation of epithelial sodium channel (ENaC) in vivo and in vitro. Respir Res 2014; 15(1): 159.
[http://dx.doi.org/10.1186/s12931-014-0159-1] [PMID: 24397246]
[42]
Liu Z, Wang D, Liu D, Liu J, Zhou G. Trimetazidine protects against LPS-induced acute lung injury through mTOR/SGK. Int J Clin Exp Med 2016; 9(7): 13950-7.
[43]
Luo X, Lin B, Gao Y, et al. Genipin attenuates mitochondrial-dependent apoptosis, endoplasmic reticulum stress, and inflammation via the PI3K/AKT pathway in acute lung injury. Int Immunopharmacol 2019; 76: 105842.
[http://dx.doi.org/10.1016/j.intimp.2019.105842] [PMID: 31466050]
[44]
Jang H, Park Y, Jang J. Serum and glucocorticoid-regulated kinase 1: Structure, biological functions, and its inhibitors. Front Pharmacol 2022; 13: 1036844.
[http://dx.doi.org/10.3389/fphar.2022.1036844] [PMID: 36457711]
[45]
Gan W, Ren J, Li T, et al. The SGK1 inhibitor EMD638683, prevents Angiotensin II–induced cardiac inflammation and fibrosis by blocking NLRP3 inflammasome activation. Biochim Biophys Acta Mol Basis Dis 2018; 1864(1): 1-10.
[http://dx.doi.org/10.1016/j.bbadis.2017.10.001] [PMID: 28986310]
[46]
D’'Antona L, Amato R, Talarico C, et al. SI113, a specific inhibitor of the Sgk1 kinase activity that counteracts cancer cell proliferation. Cell Physiol Biochem 2015; 35(5): 2006-18.
[http://dx.doi.org/10.1159/000374008] [PMID: 25871776]
[47]
Tejeswini Sen T, Kale A, Lech M, Anders HJ, Gaikwad AB. Promising novel therapeutic targets for kidney disease: Emphasis on kidney-specific proteins. Drug Discov Today 2023; 28(2): 103466.
[http://dx.doi.org/10.1016/j.drudis.2022.103466] [PMID: 36509391]
[48]
Lemmens-Gruber R, Tzotzos S. The epithelial sodium channel-an underestimated drug target. Int J Mol Sci 2023; 24(9): 7775.
[http://dx.doi.org/10.3390/ijms24097775] [PMID: 37175488]
[49]
Wang Y, Kaur G, Kumar M, Kushwah AS, Kabra A, Kainth R. Caffeic acid prevents vascular oxidative stress and atherosclerosis against atherosclerogenic diet in rats. Evid Based Complement Alternat Med 2022; 2022: 1-8.
[http://dx.doi.org/10.1155/2022/8913926] [PMID: 35069771]
[50]
Li S, Qin Q, Luo D, et al. Hesperidin ameliorates liver ischemia/reperfusion injury via activation of the Akt pathway. Mol Med Rep 2020; 22(6): 4519-30.
[http://dx.doi.org/10.3892/mmr.2020.11561] [PMID: 33174025]
[51]
Liu A, Fang H, Dahmen U, Dirsch O. Chronic lithium treatment protects against liver ischemia/reperfusion injury in rats. Liver Transpl 2013; 19(7): 762-72.
[http://dx.doi.org/10.1002/lt.23666] [PMID: 23696274]

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