Hsp60 Response in Experimental and Human Temporal Lobe Epilepsy

Overview

Journal Sci Rep

Specialty Science

Date 2015 Mar 25

PMID 25801186

Citations 18

Authors

Antonella Marino Gammazza

Roberto Colangeli

Gergely Orban

Massimo Pierucci

Giancarlo Di Gennaro

Margherita Lo Bello

Alfredo DAniello

Fabio Bucchieri

Cristoforo Pomara

Mario Valentino

Richard Muscat

Arcangelo Benigno

Giovanni Zummo

Everly Conway de Macario

Francesco Cappello

Giuseppe Di Giovanni

Alberto J L Macario

Affiliations

Soon will be listed here.

Abstract

The mitochondrial chaperonin Hsp60 is a ubiquitous molecule with multiple roles, constitutively expressed and inducible by oxidative stress. In the brain, Hsp60 is widely distributed and has been implicated in neurological disorders, including epilepsy. A role for mitochondria and oxidative stress has been proposed in epileptogenesis of temporal lobe epilepsy (TLE). Here, we investigated the involvement of Hsp60 in TLE using animal and human samples. Hsp60 immunoreactivity in the hippocampus, measured by Western blotting and immunohistochemistry, was increased in a rat model of TLE. Hsp60 was also increased in the hippocampal dentate gyrus neurons somata and neuropil and hippocampus proper (CA3, CA1) of the epileptic rats. We also determined the circulating levels of Hsp60 in epileptic animals and TLE patients using ELISA. The epileptic rats showed circulating levels of Hsp60 higher than controls. Likewise, plasma post-seizure Hsp60 levels in patients were higher than before the seizure and those of controls. These results demonstrate that Hsp60 is increased in both animals and patients with TLE in affected tissues, and in plasma in response to epileptic seizures, and point to it as biomarker of hippocampal stress potentially useful for diagnosis and patient management.

Citing Articles

The Rise of Fentanyl: Molecular Aspects and Forensic Investigations.

Barletta C, Di Natale V, Esposito M, Chisari M, Cocimano G, Di Mauro L Int J Mol Sci. 2025; 26(2).

PMID: 39859160 PMC: 11765396. DOI: 10.3390/ijms26020444.

Exploring the Gene Expression and Plasma Protein Levels of HSP90, HSP60, and GDNF in Multiple Sclerosis Patients and Healthy Controls.

Sokolowski I, Kucharska-Lusina A, Miller E, Poplawski T, Majsterek I Curr Issues Mol Biol. 2024; 46(10):11668-11680.

PMID: 39451573 PMC: 11505768. DOI: 10.3390/cimb46100693.

Ischemic stroke outcome after promoting CD4+CD25+ Treg cell migration through CCR4 overexpression in a tMCAO animal model.

Lee S, Kim J, You J, Hyun Y, Kim J, Lee J Sci Rep. 2024; 14(1):10201.

PMID: 38702399 PMC: 11068779. DOI: 10.1038/s41598-024-60358-2.

Whole-Blood Gene Expression Profile After Hypoxic-Ischemic Encephalopathy.

Montaldo P, Burgod C, Herberg J, Kaforou M, Cunnington A, Mejias A JAMA Netw Open. 2024; 7(2):e2354433.

PMID: 38306098 PMC: 10837749. DOI: 10.1001/jamanetworkopen.2023.54433.

The role of molecular chaperones in the mechanisms of epileptogenesis.

Davletshin A, Matveeva A, Poletaeva I, Evgenev M, Garbuz D Cell Stress Chaperones. 2023; 28(6):599-619.

PMID: 37755620 PMC: 10746656. DOI: 10.1007/s12192-023-01378-1.

References

Orban G, Bombardi C, Marino Gammazza A, Colangeli R, Pierucci M, Pomara C . Role(s) of the 5-HT2C receptor in the development of maximal dentate activation in the hippocampus of anesthetized rats. CNS Neurosci Ther. 2014; 20(7):651-61. PMC: 6493041. DOI: 10.1111/cns.12285. View

Orban G, Pierucci M, Benigno A, Pessia M, Galati S, Valentino M . High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo. Exp Brain Res. 2013; 230(4):441-51. DOI: 10.1007/s00221-013-3594-1. View

Sarangi U, Singh M, Abhijnya K, Reddy L, Prasad B, Pitke V . Hsp60 chaperonin acts as barrier to pharmacologically induced oxidative stress mediated apoptosis in tumor cells with differential stress response. Drug Target Insights. 2013; 7:35-51. PMC: 3767580. DOI: 10.4137/DTI.S12513. View

Willmore L, Ueda Y . Posttraumatic epilepsy: hemorrhage, free radicals and the molecular regulation of glutamate. Neurochem Res. 2008; 34(4):688-97. DOI: 10.1007/s11064-008-9841-3. View

Liefferinge J, Massie A, Portelli J, Di Giovanni G, Smolders I . Are vesicular neurotransmitter transporters potential treatment targets for temporal lobe epilepsy?. Front Cell Neurosci. 2013; 7:139. PMC: 3757300. DOI: 10.3389/fncel.2013.00139. View

Calabrese V, Mancuso C, Ravagna A, Perluigi M, Cini C, De Marco C . In vivo induction of heat shock proteins in the substantia nigra following L-DOPA administration is associated with increased activity of mitochondrial complex I and nitrosative stress in rats: regulation by glutathione redox state. J Neurochem. 2007; 101(3):709-17. DOI: 10.1111/j.1471-4159.2006.04367.x. View

Campanella C, Gammazza A, Mularoni L, Cappello F, Zummo G, Di Felice V . A comparative analysis of the products of GROEL-1 gene from Chlamydia trachomatis serovar D and the HSP60 var1 transcript from Homo sapiens suggests a possible autoimmune response. Int J Immunogenet. 2009; 36(1):73-8. DOI: 10.1111/j.1744-313X.2008.00819.x. View

Chang C, Lui C, Lee C, Chen S, Chang W, Lu C . Clinical significance of serological biomarkers and neuropsychological performances in patients with temporal lobe epilepsy. BMC Neurol. 2012; 12:15. PMC: 3342103. DOI: 10.1186/1471-2377-12-15. View

Campanella C, Bucchieri F, Ardizzone N, Gammazza A, Montalbano A, Ribbene A . Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells. Eur J Histochem. 2008; 52(4):221-8. DOI: 10.4081/1220. View

10.

Bukau B, Horwich A . The Hsp70 and Hsp60 chaperone machines. Cell. 1998; 92(3):351-66. DOI: 10.1016/s0092-8674(00)80928-9. View

11.

Wu Y, Wu S, Lee W, Wei Y . Mitochondrial respiratory dysfunction-elicited oxidative stress and posttranslational protein modification in mitochondrial diseases. Ann N Y Acad Sci. 2010; 1201:147-56. DOI: 10.1111/j.1749-6632.2010.05631.x. View

12.

Kim Y, Kim J, Ko A, Kang T . Reduction in heat shock protein 90 correlates to neuronal vulnerability in the rat piriform cortex following status epilepticus. Neuroscience. 2013; 255:265-77. DOI: 10.1016/j.neuroscience.2013.09.050. View

13.

Marino Gammazza A, Bucchieri F, Grimaldi L, Benigno A, de Macario E, Macario A . The molecular anatomy of human Hsp60 and its similarity with that of bacterial orthologs and acetylcholine receptor reveal a potential pathogenetic role of anti-chaperonin immunity in myasthenia gravis. Cell Mol Neurobiol. 2012; 32(6):943-7. PMC: 11498446. DOI: 10.1007/s10571-011-9789-8. View

14.

Bidmon H, Gorg B, Palomero-Gallagher N, Behne F, Lahl R, Pannek H . Heat shock protein-27 is upregulated in the temporal cortex of patients with epilepsy. Epilepsia. 2004; 45(12):1549-59. DOI: 10.1111/j.0013-9580.2004.14904.x. View

15.

Parnas A, Nisemblat S, Weiss C, Levy-Rimler G, Pri-Or A, Zor T . Identification of elements that dictate the specificity of mitochondrial Hsp60 for its co-chaperonin. PLoS One. 2012; 7(12):e50318. PMC: 3514286. DOI: 10.1371/journal.pone.0050318. View

16.

Ravizza T, Gagliardi B, Noe F, Boer K, Aronica E, Vezzani A . Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy. Neurobiol Dis. 2007; 29(1):142-60. DOI: 10.1016/j.nbd.2007.08.012. View

17.

Czarnecka A, Campanella C, Zummo G, Cappello F . Mitochondrial chaperones in cancer: from molecular biology to clinical diagnostics. Cancer Biol Ther. 2006; 5(7):714-20. DOI: 10.4161/cbt.5.7.2975. View

18.

Yang T, Hsu C, Liao W, Chuang J . Heat shock protein 70 expression in epilepsy suggests stress rather than protection. Acta Neuropathol. 2007; 115(2):219-30. DOI: 10.1007/s00401-007-0297-3. View

19.

Stringer J, Agarwal K, Dure L . Is cell death necessary for hippocampal mossy fiber sprouting?. Epilepsy Res. 1997; 27(1):67-76. DOI: 10.1016/s0920-1211(97)01025-5. View

20.

Xie J, Zhu H, Guo L, Ruan Y, Wang L, Sun L . Lectin-like oxidized low-density lipoprotein receptor-1 delivers heat shock protein 60-fused antigen into the MHC class I presentation pathway. J Immunol. 2010; 185(4):2306-13. DOI: 10.4049/jimmunol.0903214. View