Extracellular Hsp90α stimulates a unique innate gene profile in microglial cells with simultaneous activation of Nrf2 and protection from oxidative stress.

Amyloid beta-Peptides / toxicity Culture Media, Conditioned / pharmacology HSP90 Heat-Shock Proteins Heat-Shock Proteins / metabolism Humans Lipopolysaccharides / metabolism Microglia NF-E2-Related Factor 2 / genetics NF-kappa B / metabolism Neurodegenerative Diseases / metabolism Nitric Oxide / metabolism Oxidative Stress
Amyloid-beta Extracellular HSPs Hsp90 Inflammation Marco Microglia NF-kB Nrf2

Journal

Cell stress & chaperones
ISSN: 1466-1268
Titre abrégé: Cell Stress Chaperones
Pays: Netherlands
ID NLM: 9610925

Informations de publication

Date de publication:
09 2022
Historique:
received: 01 03 2022
accepted: 15 05 2022
revised: 01 05 2022
pubmed: 11 6 2022
medline: 23 9 2022
entrez: 10 6 2022
Statut: ppublish

Résumé

Delivery of exogenous heat shock protein 90α (Hsp90α) and/or its induced expression in neural tissues has been suggested as a potential strategy to combat neurodegenerative disease. However, within a neurodegenerative context, a pro-inflammatory response to extracellular Hsp90α (eHsp90α) could undermine strategies to use it for therapeutic intervention. The aim of this study was to investigate the biological effects of eHsp90α on microglial cells, the primary mediators of inflammatory responses in the brain. Transcriptomic profiling by RNA-seq of primary microglia and the cultured EOC2 microglial cell line treated with eHsp90α showed the chaperone to stimulate activation of innate immune responses in microglia that were characterized by an increase in NF-kB-regulated genes. Further characterization showed this response to be substantially lower in amplitude than the effects of other inflammatory stimuli such as fibrillar amyloid-β (fAβ) or lipopolysaccharide (LPS). Additionally, the toxicity of conditioned media obtained from microglia treated with fAβ was attenuated by addition of eHsp90α. Using a co-culture system of microglia and hippocampal neuronal cell line HT22 cells separated by a chamber insert, the neurotoxicity of medium conditioned by microglia treated with fAβ was reduced when eHsp90α was also added. Mechanistically, eHsp90α was shown to activate Nrf2, a response which attenuated fAβ-induced nitric oxide production. The data thus suggested that eHsp90α protects against fAβ-induced oxidative stress. We also report eHsp90α to induce expression of macrophage receptor with collagenous structure (Marco), which would permit receptor-mediated endocytosis of fAβ.

Identifiants

DOI: 10.1007/s12192-022-01279-9 PMID: 35689138 PMC: PMC9485360
pubmed: 35689138
doi: 10.1007/s12192-022-01279-9
pii: 10.1007/s12192-022-01279-9
pmc: PMC9485360
doi:

Substances chimiques

Amyloid beta-Peptides 0
Culture Media, Conditioned 0
HSP90 Heat-Shock Proteins 0
HSP90AA2P protein, human 0
Heat-Shock Proteins 0
Lipopolysaccharides 0
NF-E2-Related Factor 2 0
NF-kappa B 0
NFE2L2 protein, human 0
Nitric Oxide 31C4KY9ESH

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

461-478

Subventions

Organisme : NIAID NIH HHS
ID : R01 AI143887
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.

Références

EMBO J. 2012 Nov 5;31(21):4221-35
pubmed: 22990239
J Biol Chem. 2002 Nov 8;277(45):42769-74
pubmed: 12198130
Genetics. 2002 Jul;161(3):1101-12
pubmed: 12136014
Bioinformatics. 2010 Jan 1;26(1):139-40
pubmed: 19910308
Cell Signal. 2010 Sep;22(9):1282-90
pubmed: 20363318
Sci Transl Med. 2016 Sep 7;8(355):355ra118
pubmed: 27605553
J Biol Chem. 2005 Oct 14;280(41):34908-16
pubmed: 16051598
Front Immunol. 2016 Apr 25;7:159
pubmed: 27199984
OMICS. 2012 May;16(5):284-7
pubmed: 22455463
J Biol Chem. 2005 Aug 26;280(34):30406-15
pubmed: 15987691
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Glia. 2002 Nov;40(2):140-155
pubmed: 12379902
Circulation. 2016 Oct 4;134(14):1039-1051
pubmed: 27587433
Front Neurosci. 2017 Dec 12;11:680
pubmed: 29311768
Autophagy. 2016;12(2):245-60
pubmed: 26222012
Biochim Biophys Acta. 2012 Mar;1823(3):730-41
pubmed: 21982864
Hum Mol Genet. 2017 Dec 15;26(24):4823-4835
pubmed: 29036636
Nucleic Acids Res. 2019 Jul 2;47(W1):W212-W224
pubmed: 31114921
Cells. 2020 Oct 31;9(11):
pubmed: 33142674
Immunity. 2017 Sep 19;47(3):566-581.e9
pubmed: 28930663
J Immunol. 2006 Dec 15;177(12):8604-11
pubmed: 17142759
Front Neurosci. 2017 Apr 21;11:192
pubmed: 28484363
J Neuroinflammation. 2014 Jun 03;11:98
pubmed: 24889886
Annu Rev Pharmacol Toxicol. 2003;43:233-60
pubmed: 12359864
Arch Toxicol. 2021 Jun;95(6):1943-1970
pubmed: 34003342
Front Cell Neurosci. 2018 Aug 06;12:242
pubmed: 30127723
Immunol Rev. 2018 Jan;281(1):62-73
pubmed: 29248000
Vaccine. 2006 Jun 19;24(25):5360-70
pubmed: 16714072
J Exp Biol. 2014 Jan 1;217(Pt 1):129-36
pubmed: 24353212
Curr Chem Genom Transl Med. 2015 Feb 27;9:6-16
pubmed: 25853055
Mol Cell. 2010 May 28;38(4):576-89
pubmed: 20513432
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
Mol Psychiatry. 2021 Jun;26(6):1808-1831
pubmed: 32071385
PLoS One. 2015 Apr 02;10(4):e0122529
pubmed: 25836976
Mol Oncol. 2018 Aug;12(8):1249-1263
pubmed: 29738110
Nucleic Acids Res. 2019 Jan 8;47(D1):D766-D773
pubmed: 30357393
Cancer Res. 2021 Feb 15;81(4):956-967
pubmed: 33293426
Front Mol Neurosci. 2018 Apr 27;11:144
pubmed: 29755317
Cell Stress Chaperones. 2004 Mar;9(1):88-98
pubmed: 15270081
J Immunol. 2009 Oct 1;183(7):4601-8
pubmed: 19734219
Am J Physiol Cell Physiol. 2003 Aug;285(2):C334-42
pubmed: 12700136
J Neuroinflammation. 2012 May 31;9:115
pubmed: 22651808
Cell Mol Immunol. 2020 Aug;17(8):822-833
pubmed: 32601305
Dev Neurobiol. 2007 Nov;67(13):1815-29
pubmed: 17701989
J Immunol. 2008 Sep 15;181(6):3877-86
pubmed: 18768842
Science. 2003 May 16;300(5622):1142-5
pubmed: 12750521
Methods Mol Biol. 2018;1709:233-252
pubmed: 29177664
Brain Res. 2001 Sep 28;914(1-2):66-73
pubmed: 11578598
J Neurosci Res. 2002 Jul 1;69(1):94-103
pubmed: 12111820
Nucleic Acids Res. 2003 Dec 15;31(24):e154
pubmed: 14654707
Int J Alzheimers Dis. 2012;2012:489456
pubmed: 22666621
Biochem Biophys Res Commun. 2018 May 23;499(4):797-802
pubmed: 29621548
PLoS One. 2014 Aug 04;9(8):e104148
pubmed: 25089703
J Immunol. 2010 Sep 1;185(5):2903-17
pubmed: 20686127
J Neuroimmunol. 2019 Jan 15;326:62-74
pubmed: 30502599

Auteurs

Yuka Okusha (Y)

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. yokusha@bidmc.harvard.edu.
JSPS Overseas Research Fellowship, Tokyo, 102-0083, Japan. yokusha@bidmc.harvard.edu.
ORCID: 0000-0002-1399-2294

Benjamin J Lang (BJ)

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.

Ayesha Murshid (A)

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.

Thiago J Borges (TJ)

Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 02129, USA.

Kristina M Holton (KM)

Research Computing, Harvard Medical School, Boston, MA, 02215, USA.
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, USA.

Joanne Clark-Matott (J)

Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.

Sachin Doshi (S)

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA.

Tsuneya Ikezu (T)

Department of Neuroscience, Molecular NeuroTherapeutics Laboratory, Mayo Clinic Florida, Jacksonville, FL, 32224, USA.

Stuart K Calderwood (SK)

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA. scalderw@bidmc.harvard.edu.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Peptides bêta-amyloïdes › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Équipement et fournitures › Milieux de culture › Milieux de culture conditionnés › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Chaperons moléculaires › Protéines du choc thermique › Protéines du choc thermique HSP90 › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Chaperons moléculaires › Protéines du choc thermique › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Facteurs biologiques › Toxines biologiques › Toxines bactériennes › Endotoxines › Lipopolysaccharides › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Cellules › Névroglie › Microglie › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif basique et à glissière à leucines › Facteur-2 apparenté à NF-E2 › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteur de transcription NF-kappa B › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Maladies du système nerveux › Maladies neurodégénératives › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Produits chimiques inorganiques › Composés de l'oxygène › Oxydes › Oxydes d'azote › Monoxyde d'azote › Extracellular Hsp90α stimulates a unique...
Recherchemedicale.com › Phénomènes physiologiques › Stress physiologique › Stress oxydatif › Extracellular Hsp90α stimulates a unique...