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.

Základní údaje

Originální název

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

Autoři

ROY, S. (203 Česká republika), Jaromír GUMULEC (203 Česká republika, domácí), A. KUMAR (356 Indie), Martina RAUDENSKÁ (203 Česká republika, domácí), M.H. BAIG (410 Korejská republika), Hana POLANSKÁ (203 Česká republika, domácí), Jan BALVAN (203 Česká republika, domácí), M. GUPTA (356 Indie), Petr BABULA (203 Česká republika, domácí), J. ODSTRCILIK (203 Česká republika), I. CHOI (410 Korejská republika), Ivo PROVAZNÍK (203 Česká republika, domácí) a Michal MASAŘÍK (203 Česká republika, garant, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30103 Neurosciences

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 2.219

Kód RIV

RIV/00216224:14110/17:00099080

Organizační jednotka

Lékařská fakulta

DOI

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

UT WoS

000411368500029

Klíčová slova anglicky

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

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 20. 3. 2018 15:22, Soňa Böhmová

Anotace

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.

Návaznosti

MUNI/A/1355/2016, interní kód MU

Název: Kardiovaskulární systém očima molekulární fyziologie

Investor: Masarykova univerzita, Kardiovaskulární systém očima molekulární fyziologie, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

MUNI/A/1401/2016, interní kód MU

Název: Patofyziologické biomarkery u komplexních nemocí (Akronym: Biomarkery)

Investor: Masarykova univerzita, Patofyziologické biomarkery u komplexních nemocí, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

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 a 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, roč. 7, č. 9, s. 1-9. ISSN 2162-3279. Dostupné z: 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 a 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, roč.~7, č.~9, s.~1-9. ISSN~2162-3279. Dostupné z: https://dx.doi.org/10.1002/brb3.799.

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