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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

SET overexpression in HEK293 cells regulates mitochondrial uncoupling proteins levels within a mitochondrial fission/reduced autophagic flux scenario

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Author(s):
Almeida, Luciana O. [1] ; Goto, Renata N. [1] ; Neto, Marinaldo P. C. [2] ; Sousa, Lucas O. [1] ; Curti, Carlos [2] ; Leopoldino, Andreia M. [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Dept Clin Anal Toxicol & Food Sci, Sch Pharmaceut Sci Ribeirao Preto, BR-14040603 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Dept Chem & Phys, Sch Pharmaceut Sci Ribeirao Preto, BR-14040603 Ribeirao Preto, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Biochemical and Biophysical Research Communications; v. 458, n. 2, p. 300-306, MAR 6 2015.
Web of Science Citations: 5
Abstract

We hypothesized that SET, a protein accumulated in some cancer types and Alzheimer disease, is involved in cell death through mitochondrial mechanisms. We addressed the mRNA and protein levels of the mitochondrial uncoupling proteins UCPI, UCP2 and UCP3 (S and L isoforms) by quantitative real-time PCR and immunofluorescence as well as other mitochondrial involvements, in HEK293 cells overexpressing the SET protein (HEK293/SET), either in the presence or absence of oxidative stress induced by the pro-oxidant t-butyl hydroperoxide (t-BHP). SET overexpression in HEK293 cells decreased UCP1 and increased UCP2 and UCP3 (S/L) mRNA and protein levels, whilst also preventing lipid peroxidation and decreasing the content of cellular ATP. SET overexpression also (i) decreased the area of mitochondria and increased the number of organelles and lysosomes, (ii) increased mitochondrial fission, as demonstrated by increased FIS1 mRNA and FIS-1 protein levels, an apparent accumulation of DRP-1 protein, and an increase in the VDAC protein level, and (iii) reduced autophagic flux, as demonstrated by a decrease in LC3B lipidation (LC3B-II) in the presence of chloroquine. Therefore, SET overexpression in HEK293 cells promotes mitochondrial fission and reduces autophagic flux in apparent association with up-regulation of UCP2 and UCP3; this implies a potential involvement in cellular processes that are deregulated such as in Alzheimer's disease and cancer. (C) 2015 Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 09/52228-0 - Studies on resistance to apoptosis in cancer, head/neck model: signaling via with emphasis on PIP3-Akt/SET, oxidative stress, mitochondria and relationships
Grantee:Carlos Curti
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/01355-7 - In vitro and in vivo study of new compounds: with target-specific (hnRNP K) or action in the mitochondria for use as antitumor oral carcinoma or as cytoprotective in non-tumor cell
Grantee:Renata Nishida Goto
Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 09/10783-7 - Molecular study of hnRNP K and SET proteins on transcription and translational proteins associated in oral tumorigenesis
Grantee:Luciana Oliveira de Almeida
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 10/20384-0 - Identification of genes, miRNAs and proteins regulated by set oncoprotein and associated on malignization and tumor progression in HNSCC using in vitro and in vivo models
Grantee:Andréia Machado Leopoldino
Support Opportunities: Regular Research Grants
FAPESP's process: 13/10898-4 - Study of the molecular mechanisms by protein SET with impact on tumorigenesis and progression of oral cancer
Grantee:Carlos Curti
Support Opportunities: Regular Research Grants