HSP70 attenuates neuronal necroptosis through the HSP90α-RIPK3 pathway following neuronal trauma.
Brain trauma
HSP70
HSP90α
Necroptosis
RIPK3
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
01
12
2022
accepted:
21
06
2023
medline:
29
8
2023
pubmed:
7
7
2023
entrez:
7
7
2023
Statut:
ppublish
Résumé
Necroptosis, a newly defined regulatable necrosis with membrane disruption, has been demonstrated to participate in trauma brain injury (TBI) related neuronal cell death. Heat shock protein 70 (HSP70) is a stress protein with neuroprotective activity, but the potential protective mechanisms are not fully understood. Here, we investigated the effects of HSP70 regulators in a cellular TBI model induced by traumatic neuronal injury (TNI) and glutamate treatment. We found that necroptosis occurred in cortical neurons after TNI and glutamate treatment. Neuronal trauma markedly upregulated HSP70 protein expression within 24 h. The results of immunostaining and lactate dehydrogenase release assay showed that necroptosis following neuronal trauma was inhibited by HSP70 activator TRC051384 (TRC), but promoted by the HSP70 inhibitor 2-phenylethyenesulfonamide (PES). In congruent, the expression and phosphorylation of receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) were differently regulated by HSP70. Furthermore, the expression of HSP90α induced by neuronal trauma was further promoted by PES but decreased by TRC. The data obtained from western blot showed that the phosphorylation of RIPK3 and MLKL induced by HSP70 inhibition were reduced by RIPK3 inhibitor GSK-872 and HSP90α inhibitor geldanamycin (GA). Similarly, inhibition of HSP90α with GA could partially prevented the increased necroptosis induced by PES. Taken together, HSP70 activation exerted protective effects against neuronal trauma via inhibition of necroptosis. Mechanistically, the HSP90α-mediated activation of RIPK3 and MLKL is involved in these effects.
Sections du résumé
BACKGROUND
BACKGROUND
Necroptosis, a newly defined regulatable necrosis with membrane disruption, has been demonstrated to participate in trauma brain injury (TBI) related neuronal cell death. Heat shock protein 70 (HSP70) is a stress protein with neuroprotective activity, but the potential protective mechanisms are not fully understood.
METHODS AND RESULTS
RESULTS
Here, we investigated the effects of HSP70 regulators in a cellular TBI model induced by traumatic neuronal injury (TNI) and glutamate treatment. We found that necroptosis occurred in cortical neurons after TNI and glutamate treatment. Neuronal trauma markedly upregulated HSP70 protein expression within 24 h. The results of immunostaining and lactate dehydrogenase release assay showed that necroptosis following neuronal trauma was inhibited by HSP70 activator TRC051384 (TRC), but promoted by the HSP70 inhibitor 2-phenylethyenesulfonamide (PES). In congruent, the expression and phosphorylation of receptor interacting protein kinase 3 (RIPK3) and mixed lineage kinase domain-like protein (MLKL) were differently regulated by HSP70. Furthermore, the expression of HSP90α induced by neuronal trauma was further promoted by PES but decreased by TRC. The data obtained from western blot showed that the phosphorylation of RIPK3 and MLKL induced by HSP70 inhibition were reduced by RIPK3 inhibitor GSK-872 and HSP90α inhibitor geldanamycin (GA). Similarly, inhibition of HSP90α with GA could partially prevented the increased necroptosis induced by PES.
CONCLUSIONS
CONCLUSIONS
Taken together, HSP70 activation exerted protective effects against neuronal trauma via inhibition of necroptosis. Mechanistically, the HSP90α-mediated activation of RIPK3 and MLKL is involved in these effects.
Identifiants
pubmed: 37418085
doi: 10.1007/s11033-023-08619-7
pii: 10.1007/s11033-023-08619-7
doi:
Substances chimiques
Protein Kinases
EC 2.7.-
HSP70 Heat-Shock Proteins
0
RIPK3 protein, human
EC 2.7.11.1
Receptor-Interacting Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7237-7244Subventions
Organisme : National Natural Science Foundation of China
ID : 82072168
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature B.V.
Références
Wiles MD (2022) Management of traumatic brain injury: a narrative review of current evidence. Anaesthesia 77(Suppl 1):102–112
doi: 10.1111/anae.15608
pubmed: 35001375
Hu X et al (2022) Role of necroptosis in traumatic brain and spinal cord injuries. J Adv Res 40:125–134
doi: 10.1016/j.jare.2021.12.002
pubmed: 36100321
Sharp FR, Zhan X, Liu DZ (2013) Heat shock proteins in the brain: role of Hsp70, hsp 27, and HO-1 (Hsp32) and their therapeutic potential. Transl Stroke Res 4(6):685–692
doi: 10.1007/s12975-013-0271-4
pubmed: 24323422
Kim JY et al (2020) Heat shock protein 70 (HSP70) induction chaperonotherapy for neuroprotection after brain Injury. Cells 9(9):2020
doi: 10.3390/cells9092020
pmcid: 7563654
Sun Y et al (2006) The carboxyl-terminal domain of inducible Hsp70 protects from ischemic injury in vivo and in vitro. J Cereb Blood Flow Metab 26(7):937–950
doi: 10.1038/sj.jcbfm.9600246
pubmed: 16292251
Doeppner TR et al (2009) TAT-Hsp70-mediated neuroprotection and increased survival of neuronal precursor cells after focal cerebral ischemia in mice. J Cereb Blood Flow Metab 29(6):1187–1196
doi: 10.1038/jcbfm.2009.44
pubmed: 19384335
Kim JY et al (2013) The 70 kDa heat shock protein protects against experimental traumatic brain injury. Neurobiol Dis 58:289–295
doi: 10.1016/j.nbd.2013.06.012
pubmed: 23816752
pmcid: 3799906
Gu Y et al (2016) Hsp70 inducer, 17-allylamino-demethoxygeldanamycin, provides neuroprotection via anti-inflammatory effects in a rat model of traumatic brain injury. Exp Ther Med 12(6):3767–3772
doi: 10.3892/etm.2016.3821
pubmed: 28101166
pmcid: 5228277
Chen T et al (2012) Down-regulation of Homer1b/c attenuates glutamate-mediated excitotoxicity through endoplasmic reticulum and mitochondria pathways in rat cortical neurons. Free Radic Biol Med 52(1):208–217
doi: 10.1016/j.freeradbiomed.2011.10.451
pubmed: 22080088
Chen T et al (2022) Edonerpic maleate regulates glutamate receptors through CRMP2- and Arc-mediated mechanisms in response to brain trauma. Cell Death Discov 8(1):95
doi: 10.1038/s41420-022-00901-0
pubmed: 35246523
pmcid: 8897457
da Rocha AB et al (2005) Serum Hsp70 as an early predictor of fatal outcome after severe traumatic brain injury in males. J Neurotrauma 22(9):966–977
doi: 10.1089/neu.2005.22.966
pubmed: 16156712
Zurek J, Fedora M (2012) The usefulness of S100B, NSE, GFAP, NF-H, secretagogin and Hsp70 as a predictive biomarker of outcome in children with traumatic brain injury. Acta Neurochir (Wien) 154(1):93–103
doi: 10.1007/s00701-011-1175-2
pubmed: 21976236
Chio CC et al (2017) Exercise attenuates neurological deficits by stimulating a critical HSP70/NF-kappaB/IL-6/synapsin I axis in traumatic brain injury rats. J Neuroinflamm 14(1):90
doi: 10.1186/s12974-017-0867-9
Tandean S et al (2019) Protective Effects of Propolis Extract in a rat model of traumatic brain Injury via Hsp70 induction. Open Access Maced J Med Sci 7(17):2763–2766
doi: 10.3889/oamjms.2019.736
pubmed: 31844433
pmcid: 6901855
Zhang MH et al (2018) Neuroprotective effects of dexmedetomidine on traumatic brain injury: involvement of neuronal apoptosis and HSP70 expression. Mol Med Rep 17(6):8079–8086
pubmed: 29693126
pmcid: 5983975
Liu X et al (2016) Heat shock protein 70 inhibits cardiomyocyte necroptosis through repressing autophagy in myocardial ischemia/reperfusion injury. In Vitro Cell Dev Biol Anim 52(6):690–698
doi: 10.1007/s11626-016-0039-8
pubmed: 27130675
Srinivasan SR et al (2018) Heat shock protein 70 (Hsp70) suppresses RIP1-Dependent apoptotic and necroptotic cascades. Mol Cancer Res 16(1):58–68
doi: 10.1158/1541-7786.MCR-17-0408
pubmed: 28970360
Yashin DV et al (2016) The Tag7-Hsp70 cytotoxic complex induces tumor cell necroptosis via permeabilisation of lysosomes and mitochondria. Biochimie 123:32–36
doi: 10.1016/j.biochi.2016.01.007
pubmed: 26796882
Johnston AN, Wang Z (2020) HSP70 promotes MLKL polymerization and necroptosis. Mol Cell Oncol 7(5):1791561
doi: 10.1080/23723556.2020.1791561
pubmed: 32944645
pmcid: 7469681
Johnston AN et al (2020) Necroptosis-blocking compound NBC1 targets heat shock protein 70 to inhibit MLKL polymerization and necroptosis. Proc Natl Acad Sci U S A 117(12):6521–6530
doi: 10.1073/pnas.1916503117
pubmed: 32156734
pmcid: 7104336
Degterev A et al (2005) Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol 1(2):112–119
doi: 10.1038/nchembio711
pubmed: 16408008
Li X et al (2021) Metformin attenuates hypothalamic inflammation via downregulation of RIPK1-independent microglial necroptosis in diet-induced obese mice. Cell Death Discov 7(1):338
doi: 10.1038/s41420-021-00732-5
pubmed: 34750365
pmcid: 8575871
Wang L et al (2019) TRADD mediates RIPK1-independent necroptosis induced by tumor necrosis factor. Front Cell Dev Biol 7:393
doi: 10.3389/fcell.2019.00393
pubmed: 32039207
Su L et al (2014) A plug release mechanism for membrane permeation by MLKL. Structure 22(10):1489–1500
doi: 10.1016/j.str.2014.07.014
pubmed: 25220470
pmcid: 4192069
Seo J et al (2016) CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3. Nat Cell Biol 18(3):291–302
doi: 10.1038/ncb3314
pubmed: 26900751
Yong Y et al (2021) ERK1/2 mitogen-activated protein kinase mediates downregulation of intestinal tight junction proteins in heat stress-induced IBD model in pig. J Therm Biol 101:103103
doi: 10.1016/j.jtherbio.2021.103103
pubmed: 34879918
Taipale M et al (2012) Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 150(5):987–1001
doi: 10.1016/j.cell.2012.06.047
pubmed: 22939624
pmcid: 3894786
Zhou X et al (2019) Heat shock protein 90alpha-dependent B-cell-2-associated transcription factor 1 promotes hepatocellular carcinoma proliferation by regulating MYC proto-oncogene c-MYC mRNA stability. Hepatology 69(4):1564–1581
doi: 10.1002/hep.30172
pubmed: 30015413
Li D et al (2015) A cytosolic heat shock protein 90 and cochaperone CDC37 complex is required for RIP3 activation during necroptosis. Proc Natl Acad Sci USA 112(16):5017–5022
doi: 10.1073/pnas.1505244112
pubmed: 25852146
pmcid: 4413296
Lewis J et al (2000) Disruption of hsp90 function results in degradation of the death domain kinase, receptor-interacting protein (RIP), and blockage of tumor necrosis factor-induced nuclear factor-kappab activation. J Biol Chem 275(14):10519–10526
doi: 10.1074/jbc.275.14.10519
pubmed: 10744744
Wang Z et al (2018) Inhibition of HSP90alpha protects cultured neurons from oxygen-glucose deprivation induced necroptosis by decreasing RIP3 expression. J Cell Physiol 233(6):4864–4884
doi: 10.1002/jcp.26294
pubmed: 29334122
Liao LS et al (2021) The role of HSP90alpha in Methamphetamine/Hyperthermia-Induced necroptosis in rat striatal neurons. Front Pharmacol 12:716394
doi: 10.3389/fphar.2021.716394
pubmed: 34349659
pmcid: 8326403