Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role
of Testicular Gap Junctional Intercellular Communication and
Connexins

J 2019

Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins

KUBINCOVÁ, Petra, Eliška SYCHROVÁ, Jan RAŠKA, Amrita BASU, Affiefa YAWER et. al.

Základní údaje

Originální název

Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins

Autoři

KUBINCOVÁ, Petra (203 Česká republika, domácí), Eliška SYCHROVÁ (203 Česká republika, domácí), Jan RAŠKA (203 Česká republika, domácí), Amrita BASU (356 Indie, domácí), Affiefa YAWER (586 Pákistán, domácí), Aneta DYDOWICZOVÁ (203 Česká republika, domácí), Pavel BABICA (203 Česká republika, domácí) a Iva SOVADINOVÁ (203 Česká republika, garant, domácí)

Vydání

Toxicological sciences, OXFORD, Academic Press, 2019, 1096-6080

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30108 Toxicology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.703

Kód RIV

RIV/00216224:14310/19:00108198

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1093/toxsci/kfz023

UT WoS

000475894000009

Klíčová slova anglicky

connexins; Cx43 truncated isoforms; endocrine disruptors; gap junctional intercellular communication; polycyclic aromatic hydrocarbons; testicular cells

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 3. 4. 2020 12:45, Mgr. Marie Šípková, DiS.

Anotace

V originále

Ambient air pollution and smoking are well-documented risk factors for male infertility. Prevalent air pollutants and cigarette smoke components, polycyclic aromatic hydrocarbons (PAHs), are environmental and occupational toxicants that act as chemicals disrupting endocrine regulation and reproductive potential in males. Testicular gap junctional intercellular communication (GJIC) is critical for normal development and function of testicular tissue, thus we assessed GJIC as a process potentially targeted by PAHs in testes. Lower MW PAHs with a bay or bay-like region rapidly dysregulated GJIC in Leydig TM3 cells by relocalization of major testicular gap junctional protein connexin 43 (Cx43) from plasma membrane to cytoplasm. This was associated with colocalization between Cx43 and ubiquitin in intracellular compartments, but without any effect on Cx43 degradation rate or steady-state Cx43 mRNA levels. A longer exposure to active PAHs decreased steady-state levels of full-length Cx43 protein and its 2 N-truncated isoforms. Inhibition of GJIC by PAHs, similarly to a prototypic GJIC-inhibitor TPA, was mediated via the MAP kinase-Erk1/2 and PKC pathways. Polycyclic aromatic hydrocarbon-induced GJIC dysregulation in testes was cell-type-specific because neither PAH dysregulated GJIC in Sertoli TM4 cells, despite PAHs were rapidly taken up by both Leydig TM3 as well as Sertoli TM4 cells. Because TPA effectively dysregulated GJIC in both testicular cell types, a unique regulator of GJIC targeted by PAHs might exist in Leydig TM3 cells. Our results indicate that PAHs could be a potential etiological agent contributing to reproductive dysfunctions in males through an impairment of testicular GJIC and junctional and/or nonjunctional functions of Cx43.

Návaznosti

EF16_013/0001761, projekt VaV

Název: RECETOX RI

GJ16-10775Y, projekt VaV

Název: Mezibuněčná komunikace zprostředkovaná mezerovými spoji jako cíl endokrinních disruptorů v testikulárních buňkách

Investor: Grantová agentura ČR, Mezibuněčná komunikace zprostředkovaná mezerovými spoji jako cíl endokrinních disruptorů v testikulárních buňkách

LM2015051, projekt VaV

Název: Centrum pro výzkum toxických látek v prostředí (Akronym: RECETOX RI)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Výzkumná infrastruktura RECETOX

Citovat

KUBINCOVÁ, Petra, Eliška SYCHROVÁ, Jan RAŠKA, Amrita BASU, Affiefa YAWER, Aneta DYDOWICZOVÁ, Pavel BABICA a Iva SOVADINOVÁ. Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins. Toxicological sciences. OXFORD: Academic Press, 2019, roč. 169, č. 1, s. 70-83. ISSN 1096-6080. Dostupné z: https://dx.doi.org/10.1093/toxsci/kfz023.

@article{1639239,
   author = {Kubincová, Petra and Sychrová, Eliška and Raška, Jan and Basu, Amrita and Yawer, Affiefa and Dydowiczová, Aneta and Babica, Pavel and Sovadinová, Iva},
   article_location = {OXFORD},
   article_number = {1},
   doi = {http://dx.doi.org/10.1093/toxsci/kfz023},
   keywords = {connexins; Cx43 truncated isoforms; endocrine disruptors; gap junctional intercellular communication; polycyclic aromatic hydrocarbons; testicular cells},
   language = {eng},
   issn = {1096-6080},
   journal = {Toxicological sciences},
   title = {Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins},
   url = {http://dx.doi.org/10.1093/toxsci/kfz023},
   volume = {169},
   year = {2019}
}

TY  - JOUR
ID  - 1639239
AU  - Kubincová, Petra - Sychrová, Eliška - Raška, Jan - Basu, Amrita - Yawer, Affiefa - Dydowiczová, Aneta - Babica, Pavel - Sovadinová, Iva
PY  - 2019
TI  - Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins
JF  - Toxicological sciences
VL  - 169
IS  - 1
SP  - 70-83
EP  - 70-83
PB  - Academic Press
SN  - 10966080
KW  - connexins
KW  - Cx43 truncated isoforms
KW  - endocrine disruptors
KW  - gap junctional intercellular communication
KW  - polycyclic aromatic hydrocarbons
KW  - testicular cells
UR  - http://dx.doi.org/10.1093/toxsci/kfz023
L2  - http://dx.doi.org/10.1093/toxsci/kfz023
N2  - Ambient air pollution and smoking are well-documented risk factors for male infertility. Prevalent air pollutants and cigarette smoke components, polycyclic aromatic hydrocarbons (PAHs), are environmental and occupational toxicants that act as chemicals disrupting endocrine regulation and reproductive potential in males. Testicular gap junctional intercellular communication (GJIC) is critical for normal development and function of testicular tissue, thus we assessed GJIC as a process potentially targeted by PAHs in testes. Lower MW PAHs with a bay or bay-like region rapidly dysregulated GJIC in Leydig TM3 cells by relocalization of major testicular gap junctional protein connexin 43 (Cx43) from plasma membrane to cytoplasm. This was associated with colocalization between Cx43 and ubiquitin in intracellular compartments, but without any effect on Cx43 degradation rate or steady-state Cx43 mRNA levels. A longer exposure to active PAHs decreased steady-state levels of full-length Cx43 protein and its 2 N-truncated isoforms. Inhibition of GJIC by PAHs, similarly to a prototypic GJIC-inhibitor TPA, was mediated via the MAP kinase-Erk1/2 and PKC pathways. Polycyclic aromatic hydrocarbon-induced GJIC dysregulation in testes was cell-type-specific because neither PAH dysregulated GJIC in Sertoli TM4 cells, despite PAHs were rapidly taken up by both Leydig TM3 as well as Sertoli TM4 cells. Because TPA effectively dysregulated GJIC in both testicular cell types, a unique regulator of GJIC targeted by PAHs might exist in Leydig TM3 cells. Our results indicate that PAHs could be a potential etiological agent contributing to reproductive dysfunctions in males through an impairment of testicular GJIC and junctional and/or nonjunctional functions of Cx43.
ER  -

KUBINCOVÁ, Petra, Eliška SYCHROVÁ, Jan RAŠKA, Amrita BASU, Affiefa YAWER, Aneta DYDOWICZOVÁ, Pavel BABICA a Iva SOVADINOVÁ. Polycyclic Aromatic Hydrocarbons and Endocrine Disruption: Role of Testicular Gap Junctional Intercellular Communication and Connexins. \textit{Toxicological sciences}. OXFORD: Academic Press, 2019, roč.~169, č.~1, s.~70-83. ISSN~1096-6080. Dostupné z: https://dx.doi.org/10.1093/toxsci/kfz023.

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