The effect of Benzothiazolone-2 on the expression of
Metallothionein-3 in modulating Alzheimer's disease

J 2017

The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease

ROY, S., Jaromír GUMULEC, A. KUMAR, Martina RAUDENSKÁ, M.H. BAIG et. al.

Basic information

Original name

The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease

Authors

ROY, S. (203 Czech Republic), Jaromír GUMULEC (203 Czech Republic, belonging to the institution), A. KUMAR (356 India), Martina RAUDENSKÁ (203 Czech Republic, belonging to the institution), M.H. BAIG (410 Republic of Korea), Hana POLANSKÁ (203 Czech Republic, belonging to the institution), Jan BALVAN (203 Czech Republic, belonging to the institution), M. GUPTA (356 India), Petr BABULA (203 Czech Republic, belonging to the institution), J. ODSTRCILIK (203 Czech Republic), I. CHOI (410 Republic of Korea), Ivo PROVAZNÍK (203 Czech Republic, belonging to the institution) and Michal MASAŘÍK (203 Czech Republic, guarantor, belonging to the institution)

Edition

Brain and Behavior, Hoboken, John Wiley and Sons Inc. 2017, 2162-3279

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30103 Neurosciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 2.219

RIV identification code

RIV/00216224:14110/17:00099080

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1002/brb3.799

UT WoS

000411368500029

Keywords in English

Alzheimer's disease; flow cytometry; immunodetection; metallothionein-3; molecular dynamics; qRT-PCR

Abstract

V originále

Introduction: Metallothioneins (MTs) are a class of ubiquitously occurring low-molecular-weight cysteine- and metal-rich proteins containing sulfur-based metal clusters. MT-3 exhibits neuro-inhibitory activity. The possibility to enhance the expression of MT-3 or protect it from degradation is an attractive therapeutic target, because low levels of MT-3 were found in brains of Alzheimer's disease (AD) patients. Objectives: The primary objective of this study was to test an enhancement of MT-3 cellular concentration after MT-3 binding treatment, which could prevent MT-3 degradation. Methods: MTT assay, flow-cytometry, fluorescence microscopy, quantitative real-time polymerase chain reaction, and immunodetection of MT3 were used for analysis of effect of STOCK1N-26544, STOCK1N-26929, and STOCK1N-72593 on immortalized human microglia-SV40 cell line. Results: All three tested compounds enhanced concentration of MT-3 protein in cells and surprisingly also mRNA concentration. IC50 values of tested molecules exceeded about ten times the concentration that was needed for induction of MT-3 expression. The tested compound Benzothiazolone-2 enhanced apoptosis and necrosis, but it was not of severe effect. About 80% of cells were still viable. There was no serious ROS-generation and no severe decrease in mitochondria numbers or stress induced endoplasmic reticulum changes after test treatments. The selected compound showed stable hydrophobic and electrostatic interaction during MT-3 ligand interaction. Conclusion: Benzothiazolone-2 compounds significantly enhanced MT-3 protein and mRNA levels. The compounds can be looked upon as one of the probable lead compounds for future drug designing experiments in the treatment of Alzheimer's disease.

Links

MUNI/A/1355/2016, interní kód MU

Name: Kardiovaskulární systém očima molekulární fyziologie

Investor: Masaryk University, Category A

MUNI/A/1401/2016, interní kód MU

Name: Patofyziologické biomarkery u komplexních nemocí (Acronym: Biomarkery)

Investor: Masaryk University, Category A

Citovat

ROY, S., Jaromír GUMULEC, A. KUMAR, Martina RAUDENSKÁ, M.H. BAIG, Hana POLANSKÁ, Jan BALVAN, M. GUPTA, Petr BABULA, J. ODSTRCILIK, I. CHOI, Ivo PROVAZNÍK and Michal MASAŘÍK. The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease. Brain and Behavior. Hoboken: John Wiley and Sons Inc., 2017, vol. 7, No 9, p. 1-9. ISSN 2162-3279. Available from: https://dx.doi.org/10.1002/brb3.799.

@article{1401266,
   author = {Roy, S. and Gumulec, Jaromír and Kumar, A. and Raudenská, Martina and Baig, M.H. and Polanská, Hana and Balvan, Jan and Gupta, M. and Babula, Petr and Odstrcilik, J. and Choi, I. and Provazník, Ivo and Masařík, Michal},
   article_location = {Hoboken},
   article_number = {9},
   doi = {http://dx.doi.org/10.1002/brb3.799},
   keywords = {Alzheimer's disease; flow cytometry; immunodetection; metallothionein-3; molecular dynamics; qRT-PCR},
   language = {eng},
   issn = {2162-3279},
   journal = {Brain and Behavior},
   title = {The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease},
   volume = {7},
   year = {2017}
}

TY  - JOUR
ID  - 1401266
AU  - Roy, S. - Gumulec, Jaromír - Kumar, A. - Raudenská, Martina - Baig, M.H. - Polanská, Hana - Balvan, Jan - Gupta, M. - Babula, Petr - Odstrcilik, J. - Choi, I. - Provazník, Ivo - Masařík, Michal
PY  - 2017
TI  - The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease
JF  - Brain and Behavior
VL  - 7
IS  - 9
SP  - 1-9
EP  - 1-9
PB  - John Wiley and Sons Inc.
SN  - 21623279
KW  - Alzheimer's disease
KW  - flow cytometry
KW  - immunodetection
KW  - metallothionein-3
KW  - molecular dynamics
KW  - qRT-PCR
N2  - Introduction: Metallothioneins (MTs) are a class of ubiquitously occurring low-molecular-weight cysteine- and metal-rich proteins containing sulfur-based metal clusters. MT-3 exhibits neuro-inhibitory activity. The possibility to enhance the expression of MT-3 or protect it from degradation is an attractive therapeutic target, because low levels of MT-3 were found in brains of Alzheimer's disease (AD) patients. Objectives: The primary objective of this study was to test an enhancement of MT-3 cellular concentration after MT-3 binding treatment, which could prevent MT-3 degradation. Methods: MTT assay, flow-cytometry, fluorescence microscopy, quantitative real-time polymerase chain reaction, and immunodetection of MT3 were used for analysis of effect of STOCK1N-26544, STOCK1N-26929, and STOCK1N-72593 on immortalized human microglia-SV40 cell line. Results: All three tested compounds enhanced concentration of MT-3 protein in cells and surprisingly also mRNA concentration. IC50 values of tested molecules exceeded about ten times the concentration that was needed for induction of MT-3 expression. The tested compound Benzothiazolone-2 enhanced apoptosis and necrosis, but it was not of severe effect. About 80% of cells were still viable. There was no serious ROS-generation and no severe decrease in mitochondria numbers or stress induced endoplasmic reticulum changes after test treatments. The selected compound showed stable hydrophobic and electrostatic interaction during MT-3 ligand interaction. Conclusion: Benzothiazolone-2 compounds significantly enhanced MT-3 protein and mRNA levels. The compounds can be looked upon as one of the probable lead compounds for future drug designing experiments in the treatment of Alzheimer's disease.
ER  -

ROY, S., Jaromír GUMULEC, A. KUMAR, Martina RAUDENSKÁ, M.H. BAIG, Hana POLANSKÁ, Jan BALVAN, M. GUPTA, Petr BABULA, J. ODSTRCILIK, I. CHOI, Ivo PROVAZNÍK and Michal MASAŘÍK. The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease. \textit{Brain and Behavior}. Hoboken: John Wiley and Sons Inc., 2017, vol.~7, No~9, p.~1-9. ISSN~2162-3279. Available from: https://dx.doi.org/10.1002/brb3.799.

Detailed Information on Publication Record