Helicobacter pylori infection induces autophagy via ILK regulation of NOXs-ROS-Nrf2/HO-1-ROS loop.
Autophagy
HO-1
Helicobacter pylori
NOX
Nrf2
ROS
Journal
World journal of microbiology & biotechnology
ISSN: 1573-0972
Titre abrégé: World J Microbiol Biotechnol
Pays: Germany
ID NLM: 9012472
Informations de publication
Date de publication:
21 Aug 2023
21 Aug 2023
Historique:
received:
04
08
2022
accepted:
21
07
2023
medline:
22
8
2023
pubmed:
21
8
2023
entrez:
20
8
2023
Statut:
epublish
Résumé
Reactive oxygen species (ROS) can regulate the occurrence of autophagy, and effective control of the balance between ROS and autophagy may be an important strategy for Helicobacter pylori induced gastric-related diseases. In this study, infection with H. pylori led to a lower level of ILK phosphorylation and increased ROS generation. Knockdown of ILK enhanced total ROS generation, and upregulated NADPH oxidase (NOX) subunit p22-phox levels. Inhibition of NOXs affected total ROS generation. The inhibition of NOX and ROS generation reduced Nrf2 and HO-1 levels, and knockdown of ILK significantly enhanced Nrf2 levels in H. pylori-infected GES-1 cells. Activation of Nrf2 by DMF decreased ROS levels. Therefore, NOX-dependent ROS production regulated by ILK was essential for activation of Nrf2/HO-1 signaling pathways in H. pylori-infected GES-1 cells. Beclin1, ATG5 and LC3B-II levels were higher both in H. pylori-infected and ILK-knockdown GES-1 cells. In NAC-pretreated GES-1 cells infected with H. pylori, the LC3B-II level was decreased compared to that in cells after H. pylori infection alone. Stable low expression of ILK with further knockdown of Beclin1 or ATG5 significantly reduced LC3B-II levels in GES-1 cells, while with the addition of the autophagy inhibitor chloroquine (CQ), LC3B-II and p62 protein levels were both remarkably upregulated. H. pylori accelerated the accumulation of ROS and further led to the induction of ROS-mediated autophagy by inhibiting ILK levels. Together, these results indicate that H. pylori infection manipulates the NOX-ROS-Nrf2/HO-1-ROS loop to control intracellular oxygen stress and further induced ROS-mediated autophagy by inhibiting ILK levels.
Identifiants
pubmed: 37599292
doi: 10.1007/s11274-023-03710-4
pii: 10.1007/s11274-023-03710-4
doi:
Substances chimiques
NF-E2-Related Factor 2
0
Reactive Oxygen Species
0
Beclin-1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
284Subventions
Organisme : National Natural Science Foundation of China
ID : 82172560
Organisme : Department of Education of Shandong Province under Grant
ID : 2019KJK012
Organisme : Taishan Scholars Program of Shandong Province, China
ID : tsqn202211229
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Abraham NG, Kappas A (2008) Pharmacological and clinical aspects of heme oxygenase. Pharmacol Rev 60(1):79–127. https://doi.org/10.1124/pr.107.07104
doi: 10.1124/pr.107.07104
pubmed: 18323402
Butcher LD, den Hartog G, Ernst PB, Crowe SE (2017) Oxidative stress resulting from Helicobacter pylori infection contributes to gastric carcinogenesis. Cell Mol Gastroenterol Hepatol 3(3):316–322. https://doi.org/10.1016/j.jcmgh.2017.02.002
doi: 10.1016/j.jcmgh.2017.02.002
pubmed: 28462373
pmcid: 5404027
Chen YF, Liu H, Luo XJ, Zhao Z, Zou ZY, Li J, Lin XJ, Liang Y (2017) The roles of reactive oxygen species (ROS) and autophagy in the survival and death of leukemia cells. Crit Rev Oncol Hematol 112:21–30. https://doi.org/10.1016/j.critrevonc.2017.02.004
doi: 10.1016/j.critrevonc.2017.02.004
pubmed: 28325262
Dedhar S (2000) Cell-substrate interactions and signaling through ILK. Curr Opin Cell Biol 12(2):250–256. https://doi.org/10.1016/s0955-0674(99)00083-6
doi: 10.1016/s0955-0674(99)00083-6
pubmed: 10712922
Ding SZ, Minohara Y, Fan XJ, Wang J, Reyes VE, Patel J, Dirden-Kramer B, Boldogh I, Ernst PB, Crowe SE (2007) Helicobacter pylori infection induces oxidative stress and programmed cell death in human gastric epithelial cells. Infect Immun 75(8):4030–4039. https://doi.org/10.1128/IAI.00172-07
doi: 10.1128/IAI.00172-07
pubmed: 17562777
pmcid: 1952011
Gassen NC, Niemeyer D, Muth D, Corman VM, Martinelli S, Gassen A et al (2019) SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-coronavirus infection. Nat Commun 10(1):5770. https://doi.org/10.1038/s41467-019-13659-4
doi: 10.1038/s41467-019-13659-4
pubmed: 31852899
pmcid: 6920372
Ghatak S, Morgner J, Wickström SA (2013) ILK: a pseudokinase with a unique function in the integrin-actin linkage. Biochem Soc Trans 41(4):995–1001. https://doi.org/10.1042/BST20130062
doi: 10.1042/BST20130062
pubmed: 23863169
Graness A, Giehl K, Goppelt-Struebe M (2006) Differential involvement of the integrin-linked kinase (ILK) in RhoA-dependent rearrangement of F-actin fibers and induction of connective tissue growth factor (CTGF). Cell Signal 18(4):433–440. https://doi.org/10.1016/j.cellsig.2005.05.011
doi: 10.1016/j.cellsig.2005.05.011
pubmed: 15970428
Greenfield LK, Jones NL (2013) Modulation of autophagy by Helicobacter pylori and its role in gastric carcinogenesis. Trends Microbiol 21(11):602–612. https://doi.org/10.1016/j.tim.2013.09.004
doi: 10.1016/j.tim.2013.09.004
pubmed: 24156875
Gureev AP, Popov VN, Starkov AA (2020) Crosstalk between the mTOR and Nrf2/ARE signaling pathways as a target in the improvement of long-term potentiation. Exp Neurol 328:113285. https://doi.org/10.1016/j.expneurol.2020.113285
doi: 10.1016/j.expneurol.2020.113285
pubmed: 32165256
pmcid: 7145749
Handa O, Naito Y, Yoshikawa T (2010) Helicobacter pylori: a ROS-inducing bacterial species in the stomach. Inflamm Res 59(12):997–1003. https://doi.org/10.1007/s00011-010-0245-x
doi: 10.1007/s00011-010-0245-x
pubmed: 20820854
Kast DJ, Dominguez R (2017) The cytoskeleton-autophagy connection. Curr Biol 27(8):R318–R326. https://doi.org/10.1016/j.cub.2017.02.061
doi: 10.1016/j.cub.2017.02.061
pubmed: 28441569
pmcid: 5444402
Kawahara T, Kohjima M, Kuwano Y, Mino H, Teshima-Kondo S, Takeya R, Tsunawaki S, Wada A, Sumimoto H, Rokutan K (2005) Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells. Am J Physiol Cell Physiol 288(2):C450–C457. https://doi.org/10.1152/ajpcell.00319.2004
doi: 10.1152/ajpcell.00319.2004
pubmed: 15469954
Kim YM, Kim SJ, Tatsunami R, Yamamura H, Fukai T, Ushio-Fukai M (2017) ROS-induced ROS release orchestrated by Nox4, Nox2, and mitochondria in VEGF signaling and angiogenesis. Am J Physiol Cell Physiol 312(6):C749–C764. https://doi.org/10.1152/ajpcell.00346.2016
doi: 10.1152/ajpcell.00346.2016
pubmed: 28424170
pmcid: 5494593
Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S et al (2021) Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1. Autophagy 17(1):1–382. https://doi.org/10.1080/15548627.2020.1797280
doi: 10.1080/15548627.2020.1797280
pubmed: 33634751
pmcid: 7996087
Ko SH, Rho DJ, Jeon JI, Kim YJ, Woo HA, Kim N, Kim JM (2016) Crude preparations of Helicobacter pylori outer membrane vesicles induce upregulation of heme oxygenase-1 via activating Akt-Nrf2 and mTOR-IκB kinase-NF-κB pathways in dendritic cells. Infect Immun 84(8):2162–2174. https://doi.org/10.1128/IAI.00190-16
doi: 10.1128/IAI.00190-16
pubmed: 27185786
pmcid: 4962631
Kwak HJ, Liu P, Bajrami B, Xu Y, Park SY, Nombela-Arrieta C, Mondal S, Sun Y, Zhu H, Chai L, Silberstein LE, Cheng T, Luo HR (2015) Myeloid cell-derived reactive oxygen species externally regulate the proliferation of myeloid progenitors in emergency granulopoiesis. Immunity 42(1):159–171. https://doi.org/10.1016/j.immuni.2014.12.017
doi: 10.1016/j.immuni.2014.12.017
pubmed: 25579427
pmcid: 4303526
Lee HJ, Han YM, Kim EH, Kim YJ, Hahm KB (2012) A possible involvement of Nrf2-mediated heme oxygenase-1 up-regulation in protective effect of the proton pump inhibitor pantoprazole against indomethacin-induced gastric damage in rats. BMC Gastroenterol 12:143. https://doi.org/10.1186/1471-230X-12-143
doi: 10.1186/1471-230X-12-143
pubmed: 23066659
pmcid: 3548718
Levy JMM, Towers CG, Thorburn A (2017) Targeting autophagy in cancer. Nat Rev Cancer 17(9):528–542. https://doi.org/10.1038/nrc.2017.53
doi: 10.1038/nrc.2017.53
pubmed: 28751651
Li L, Tan J, Miao Y, Lei P, Zhang Q (2015) ROS and autophagy: interactions and molecular regulatory mechanisms. Cell Mol Neurobiol 35(5):615–621. https://doi.org/10.1007/s10571-015-0166-x
doi: 10.1007/s10571-015-0166-x
pubmed: 25722131
Lu H, Li Y, Zhang T, Liu M, Chi Y, Liu S, Shi Y (2017) Salidroside reduces high-glucose-induced podocyte apoptosis and oxidative stress via upregulating heme oxygenase-1 (HO-1) expression. Med Sci Monit 23:4067–4076. https://doi.org/10.12659/msm.902806
doi: 10.12659/msm.902806
pubmed: 28831032
pmcid: 5580518
Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426. https://doi.org/10.1146/annurev-pharmtox-011112-140320
doi: 10.1146/annurev-pharmtox-011112-140320
pubmed: 23294312
pmcid: 4680839
Ma TJ, Lan DH, He SZ, Ye Z, Li P, Zhai W, Chen WQ, Huang Y, Fu Y, Sun A, Wang YB, Ye Z, Li JL, Gao Y, Yan XL, Li ZH (2018) Nrf2 protects human lens epithelial cells against H
doi: 10.1016/j.exer.2018.01.018
pubmed: 29421327
Magnani F, Mattevi A (2019) Structure and mechanisms of ROS generation by NADPH oxidases. Curr Opin Struct Biol 59:91–97. https://doi.org/10.1016/j.sbi.2019.03.001
doi: 10.1016/j.sbi.2019.03.001
pubmed: 31051297
Mizushima N, Yoshimori T (2007) How to interpret LC3 immunoblotting. Autophagy 3(6):542–545. https://doi.org/10.4161/auto.4600
doi: 10.4161/auto.4600
pubmed: 17611390
Neves KB, Rios FJ, van der Mey L, Alves-Lopes R, Cameron AC, Volpe M, Montezano AC, Savoia C, Touyz RM (2018) VEGFR (vascular endothelial growth factor receptor) inhibition induces cardiovascular damage via redox-sensitive processes. Hypertension 71(4):638–647. https://doi.org/10.1161/HYPERTENSIONAHA.117.10490
doi: 10.1161/HYPERTENSIONAHA.117.10490
pubmed: 29483228
Nishida Y, Arakawa S, Fujitani K, Yamaguchi H, Mizuta T, Kanaseki T, Komatsu M, Otsu K, Tsujimoto Y, Shimizu S (2009) Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 461(7264):654–658. https://doi.org/10.1038/nature08455
doi: 10.1038/nature08455
pubmed: 19794493
Paik JY, Lee HG, Piao JY, Kim SJ, Kim DH, Na HK, Surh YJ (2019) Helicobacter pylori infection promotes autophagy through Nrf2-mediated heme oxygenase upregulation in human gastric cancer cells. Biochem Pharmacol 162:89–97. https://doi.org/10.1016/j.bcp.2019.02.003
doi: 10.1016/j.bcp.2019.02.003
pubmed: 30731075
Ren WK, Xu YF, Wei WH, Huang P, Lian DW, Fu LJ, Yang XF, Chen FJ, Wang J, Cao HY, Deng YH (2019) Effect of patchouli alcohol on Helicobacter pylori-induced neutrophil recruitment and activation. Int Immunopharmacol 68:7–16. https://doi.org/10.1016/j.intimp.2018.12.044
doi: 10.1016/j.intimp.2018.12.044
pubmed: 30599446
Ricci V (2016) Relationship between VacA toxin and host cell autophagy in Helicobacter pylori infection of the human stomach: a few answers, many questions. Toxins (Basel) 8(7):203. https://doi.org/10.3390/toxins8070203
doi: 10.3390/toxins8070203
pubmed: 27376331
Scherz-Shouval R, Elazar Z (2011) Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci 36(1):30–38. https://doi.org/10.1016/j.tibs.2010.07.007
doi: 10.1016/j.tibs.2010.07.007
pubmed: 20728362
Shibutani ST, Saitoh T, Nowag H, Münz C, Yoshimori T (2015) Autophagy and autophagy-related proteins in the immune system. Nat Immunol 16(10):1014–1024. https://doi.org/10.1038/ni.3273
doi: 10.1038/ni.3273
pubmed: 26382870
Wang F, Meng W, Wang B, Qiao L (2014) Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett 345(2):196–202. https://doi.org/10.1016/j.canlet.2013.08.016
doi: 10.1016/j.canlet.2013.08.016
pubmed: 23981572
Xie C, Yi J, Lu J, Nie M, Huang M, Rong J, Zhu Z, Chen J, Zhou X, Li B, Chen H, Lu N, Shu X (2018) N-acetylcysteine reduces ROS-mediated oxidative DNA damage and PI3K/Akt pathway activation induced by Helicobacter pylori infection. Oxid Med Cell Longev. https://doi.org/10.1155/2018/1874985
doi: 10.1155/2018/1874985
pubmed: 30050663
pmcid: 6040290
Xie J, He X, Fang H, Liao S, Liu Y, Tian L, Niu J (2020) Identification of heme oxygenase-1 from golden pompano (Trachinotus ovatus) and response of Nrf2/HO-1 signaling pathway to copper-induced oxidative stress. Chemosphere 253:126654. https://doi.org/10.1016/j.chemosphere.2020.126654
doi: 10.1016/j.chemosphere.2020.126654
pubmed: 32464761
Yang J, Li J, Wang Q, Xing Y, Tan Z, Kang Q (2018) Novel NADPH oxidase inhibitor VAS2870 suppresses TGF-β-dependent epithelialtomesenchymal transition in retinal pigment epithelial cells. Int J Mol Med 42(1):123–130. https://doi.org/10.3892/ijmm.2018.3612
doi: 10.3892/ijmm.2018.3612
pubmed: 29620174
pmcid: 5979836
Zhang F, Chen C, Hu J, Su R, Zhang J, Han Z, Chen H, Li Y (2019) Molecular mechanism of Helicobacter pylori-induced autophagy in gastric cancer. Oncol Lett 18(6):6221–6227. https://doi.org/10.3892/ol.2019.10976
doi: 10.3892/ol.2019.10976
pubmed: 31788098
pmcid: 6865805