Mitochondrial heat shock protein mortalin as potential target for therapies based on oxidative stress.

Autor: Pagliarone AC; Lab. of Applied Immunology, Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, SP, Brazil., Castañeda ED; Lab. of Applied Immunology, Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, SP, Brazil., Santana JPP; Lab. of Applied Immunology, Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, SP, Brazil., de Oliveira CAB; Lab. of Cellular Biochemistry, Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, SP, Brazil., Robeldo TA; Lab. of Applied Immunology, Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, SP, Brazil., Teixeira FR; Lab. of Cellular Biochemistry, Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, SP, Brazil., Borra RC; Lab. of Applied Immunology, Department of Genetics and Evolution, Federal University of São Carlos, São Carlos, SP, Brazil. Electronic address: rcborra@ufscar.br.
Jazyk: angličtina
Zdroj: Photodiagnosis and photodynamic therapy [Photodiagnosis Photodyn Ther] 2021 Jun; Vol. 34, pp. 102256. Date of Electronic Publication: 2021 Mar 15.
DOI: 10.1016/j.pdpdt.2021.102256
Abstrakt: Background: Treatments based on production of reactive oxygen species for bladder cancer such as photodynamic therapy (PDT) have been marginalized due to low specificity and the existence of resistance mainly associated with the up-regulation of Heat Shock Proteins (HSPs). To overcome these barriers, the establishment of strategies combining PDTs with HSP inhibitors may be promising and the identification of HSPs involved with oxidative stress from bladder tumors in animal models represents a key step in this direction.
Materials: Thus, the present study aims to identify cytosolic and mitochondrial HSPs up expressed in murine bladder tumors and in the urothelial carcinoma cell line MB49 by qRT-PCR screening, and to analyze the importance of the activity of the HSPs associated with oxidative stress protection in the survival of the MB49 using strategy of inhibition in vitro.
Results: Results showed that both tumor tissues and MB49 cells in culture had significant overexpression of the mitochondrial HSPA9 (mortalin) and HSP60 mRNAs, while the cytosolic HSP90 was overexpressed only in the tumor. The effect of mortalin in the MB49 cells survival under oxidative stress was evaluated in vitro in presence of the specific inhibitor MKT-077 and H 2 O 2 . The findings showed that MB49 viability was permanently reduced by the MKT-077 in a dose-dependent manner by inducing apoptosis or necrosis, mainly under oxidative stress conditions.
Conclusion: Results suggest that mortalin is preferentially expressed in the MB49 cancer model and plays a key role in tumoral survival, especially under oxidative stress, making this HSP a potential target for an alternative treatment combining PDT with HSP inhibitors.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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