Suberoylanilide hydroxamic acid suppresses axonal damage and neurological dysfunction after subarachnoid hemorrhage via the HDAC1/HSP70/TDP-43 axis
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Increased focus has been placed on the role of histone deacetylase inhibitors as crucial players in subarachnoid hemorrhage (SAH) progression. Therefore, this study was designed to expand the understanding of SAH by exploring the downstream mechanism of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in SAH. The expression of TDP-43 in patients with SAH and rat models of SAH was measured. Then, western blot analysis, immunofluorescence staining, and transmission electron microscope were used to investigate the in vitro effect of TDP-43 on a neuronal cell model of SAH established by oxyhemoglobin treatment. Immunofluorescence staining and coimmunoprecipitation assays were conducted to explore the relationship among histone deacetylase 1 (HDAC1), heat shock protein 70 (HSP70), and TDP-43. Furthermore, the in vivo effect of HDAC1 on SAH was investigated in rat models of SAH established by endovascular perforation. High expression of TDP-43 in the cerebrospinal fluid of patients with SAH and brain tissues of rat models of SAH was observed, and TDP-43 accumulation in the cytoplasm and the formation of inclusion bodies were responsible for axonal damage, abnormal nuclear membrane morphology, and apoptosis in neurons. TDP-43 degradation was promoted by the HDAC1 inhibitor SAHA via the acetylation of HSP70, alleviating SAH, and this effect was verified in vivo in rat models. In conclusion, SAHA relieved axonal damage and neurological dysfunction after SAH via the HSP70 acetylation-induced degradation of TDP-43, highlighting a novel therapeutic target for SAH.
Abstract
Increased focus has been placed on the role of histone deacetylase inhibitors as crucial players in subarachnoid hemorrhage (SAH) progression. Therefore, this study was designed to expand the understanding of SAH by exploring the downstream mechanism of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) in SAH. The expression of TDP-43 in patients with SAH and rat models of SAH was measured. Then, western blot analysis, immunofluorescence staining, and transmission electron microscope were used to investigate the in vitro effect of TDP-43 on a neuronal cell model of SAH established by oxyhemoglobin treatment. Immunofluorescence staining and coimmunoprecipitation assays were conducted to explore the relationship among histone deacetylase 1 (HDAC1), heat shock protein 70 (HSP70), and TDP-43. Furthermore, the in vivo effect of HDAC1 on SAH was investigated in rat models of SAH established by endovascular perforation. High expression of TDP-43 in the cerebrospinal fluid of patients with SAH and brain tissues of rat models of SAH was observed, and TDP-43 accumulation in the cytoplasm and the formation of inclusion bodies were responsible for axonal damage, abnormal nuclear membrane morphology, and apoptosis in neurons. TDP-43 degradation was promoted by the HDAC1 inhibitor SAHA via the acetylation of HSP70, alleviating SAH, and this effect was verified in vivo in rat models. In conclusion, SAHA relieved axonal damage and neurological dysfunction after SAH via the HSP70 acetylation-induced degradation of TDP-43, highlighting a novel therapeutic target for SAH.
참고문헌 (37)
- Boling, B., "Management of subarachnoid hemorrhage", Crit. Care Nurse, 39, pp.58~67 (2019)
- Ogunlaja, O. I., "Subarachnoid hemorrhage and headache", Curr. Pain. Headache Rep, 23, pp.44~ (2019)
- Long, B., "Subarachnoid hemorrhage : updates in diagnosis and management", Emerg. Med. Clin. North Am, 35, pp.803~824 (2017)
- Song, H., "Sodium", hydrogen exchanger 1 participates in early brain injury after subarachnoid hemorrhage both in vivo and in vitro via promoting neuronal apoptosis, 2019, pp.28, 985~1001
- Hall, A., "The extracranial consequences of subarachnoid hemorrhage", World Neurosurg, 109, pp.381~392 (2018)
- Venti, M., "Subarachnoid and intraventricular hemorrhage", Front. Neurol. Neurosci, 30, pp.149~153 (2012)
- Liu, Z., "Effects of suberoylanilide hydroxamic acid(SAHA)combined with paclitaxel(PTX)on paclitaxel-resistant ovarian cancer cells and insights into the underlying mechanisms", Cancer Cell Int, 14, pp.112~ (2014)
- Chiaradonna, F., "Redox-mediated suberoylanilide hydroxamic acid sensitivity in breast cancer", Antioxid. Redox Signal, 23, pp.15~29 (2015)
- Sukumari-Ramesh, S., "The histone deacetylase inhibitor suberoylanilide hydroxamic acid(SAHA)confers acute neuroprotection after intracerebral hemorrhage in mice", Transl. Stroke Res, 7, pp.141~148 (2016)
- Duvic, M., "The safety profile of vorinostat(suberoylanilide hydroxamic acid)in hematologic malignancies : a review of clinical studies", Cancer Treat. Rev, 43, pp.58~66 (2016)
- Wu, L., "Inhibition of HDAC4 attenuated JNK", c-Jun-dependent neuronal apoptosis and early brain injury following subarachnoid hemorrhage by transcriptionally suppressing MKK7, 2019, pp.13, 468~
- Tsai, H. D., "Clinacanthus nutans protects cortical neurons against hypoxiainduced toxicity by downregulating HDAC1", 6, 2016, pp.18, 274~282
- Chen, S., "AMPK-HDAC5 pathway facilitates nuclear accumulation of HIF-1alpha and functional activation of HIF-1 by deacetylating Hsp70 in the cytosol", Cell Cycle, 14, pp.2520~2536 (2015)
- Shao, A., "The role and therapeutic potential of heat shock proteins in haemorrhagic stroke", J. Cell. Mol. Med, 23, pp.5846~5858 (2019)
- Lin, P. Y., "Overexpression of heat shock factor 1 maintains TAR DNA binding protein 43 solubility via induction of inducible heat shock protein 70 in cultured cells", J. Neurosci. Res, 94, pp.671~682 (2016)
- Smeltzer, S., "Hypusination of Eif5a regulates cytoplasmic TDP-43 aggregation and accumulation in a stress-induced cellular model", Biochim. Biophys. Acta Mol. Basis. Dis, 1867, pp.165939~ (2021)
- He, T., "Subarachnoid hemorrhage enhances the expression of TDP-43 in the brain of experimental rats and human subjects", Exp. Ther. Med, 16, pp.3363~3368 (2018)
- Sozen, T., "Role of interleukin-1beta in early brain injury after subarachnoid hemorrhage in mice", Stroke, 40, pp.2519~2525 (2009)
- Kooijman, E., "The rodent endovascular puncture model of subarachnoid hemorrhage : mechanisms of brain damage and therapeutic strategies", J. Neuroinflammation, 11, pp.2~ (2014)
- Chen, X., "CX3CL1", CX3CR1 axis attenuates early brain injury via promoting the delivery of exosomal microRNA-124 from neuron to microglia after subarachnoid hemorrhage, 2020, pp.17, 209~
- Li, X., "Loss of ribosomal RACK1(receptor for activated protein kinase C 1)induced by phosphorylation at T50 alleviates cerebral ischemia-reperfusion injury in rats", Stroke, 50, pp.162~171 (2019)
- Fang, Y., "Deficiency of TREK-1 potassium channel exacerbates blood-brain barrier damage and neuroinflammation after intracerebral hemorrhage in mice", J. Neuroinflammation, 16, pp.96~ (2019)
- Liu, H., "Bakuchiol attenuates oxidative stress and neuron damage by regulating Trx1", TXNIP and the phosphorylation of AMPK after subarachnoid hemorrhage in mice, 2020, pp.11, 712~
- Macdonald, R. L., "Spontaneous subarachnoid haemorrhage", Lancet, 389, pp.655~666 (2017)
- Egashira, Y., "Acute white matter injury after experimental subarachnoid hemorrhage : potential role of lipocalin 2", Stroke, 45, pp.2141~2143 (2014)
- Shao, A., "Enhancement of autophagy by histone deacetylase inhibitor trichostatin A ameliorates neuronal apoptosis after subarachnoid hemorrhage in rats", Mol. Neurobiol, 53, pp.18~27 (2016)
- Jian, X., "Trichostatin A-induced miR30a5p regulates apoptosis and proliferation of keloid fibroblasts via targeting BCL2", Mol. Med. Rep, 19, pp.5251~5262 (2019)
- Gao, J., "Pathomechanisms of TDP-43in neurodegeneration", J. Neurochem, 146, pp.7~20 (2018)
- Chou, C. C., "TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS", FTD, 2018, pp.21, 228~239
- Budini, M., "Autophagy and its impact on neurodegenerative diseases : new roles for TDP-43 and C9orf72", Front. Mol. Neurosci, 10, pp.170~ (2017)
- Cohen, T. J., "An acetylation switch controls TDP-43 function and aggregation propensity", Nat. Commun, 6, pp.5845~ (2015)
- Chang, X. L., "The role of TDP-43 in Alzheimer’s disease", Mol. Neurobiol, 53, pp.3349~3359 (2016)
- Chen, H. J., "The heat shock response plays an important role in TDP-43clearance : evidence for dysfunction in amyotrophic lateral sclerosis", Brain, 139, pp.1417~1432 (2016)
- Chen, J., "Protein acetylation", deacetylation : a potential strategy for fungal infection control, 2020, pp.11, 574736~
- Joshi, A. D., "Histone deacetylase inhibitors prevent pulmonary endothelial hyperpermeability and acute lung injury by regulating heat shock protein 90function", Am. J. Physiol. Lung Cell. Mol. Physiol, 309, pp.L1410~L1419 (2015)
- Yang, H., "HDAC inhibition reduces white matter injury after intracerebral hemorrhage", J. Cereb. Blood Flow. Metab, 41, pp.958~974 (2020)
- Li, W., "Suberoylanilide hydroxamic acid alleviates acute lung injury induced by severe hemorrhagic shock and resuscitation in rats", Shock, 54, pp.474~481 (2020)