Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap
Junctions, a Robust Cellular Response to Environmental
Toxicants, and Prevention by Resveratrol in a Rat Liver Cell
Model

J 2015

Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model

SOVADINOVÁ, Iva, Pavel BABICA, Hatice BOKE, Esha KUMAR, Andrew WILKE et. al.

Basic information

Original name

Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model

Authors

SOVADINOVÁ, Iva (203 Czech Republic, belonging to the institution), Pavel BABICA (203 Czech Republic), Hatice BOKE (840 United States of America), Esha KUMAR (840 United States of America), Andrew WILKE (840 United States of America), Joon-Suk PARK (840 United States of America), James E. TROSKO (840 United States of America) and Brad L. UPHAM (840 United States of America, guarantor)

Edition

PLOS ONE, SAN FRANCISCO (USA), Public Library of Science, 2015, 1932-6203

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30304 Public and environmental health

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.057

RIV identification code

RIV/00216224:14310/15:00086654

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1371/journal.pone.0124454

UT WoS

000355319400005

Keywords in English

Phosphatidylcholine; PLC-Induced Dysregulation; Gap Junctions; Environmental Toxicants; Rat Liver; Cell Model

Abstract

V originále

Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants work through either signaling mechanisms or both. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways. In conclusion: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap junction channels are closed by toxicants vary. Thus, accurate assessments of risk posed by toxic agents, and the role of dietary phytochemicals play in preventing or reversing the effects of these agents must take into account the specific mechanisms involved in the cancer process.

Citovat

SOVADINOVÁ, Iva, Pavel BABICA, Hatice BOKE, Esha KUMAR, Andrew WILKE, Joon-Suk PARK, James E. TROSKO and Brad L. UPHAM. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model. PLOS ONE. SAN FRANCISCO (USA): Public Library of Science, 2015, vol. 10, No 5, p. "nestránkováno", 16 pp. ISSN 1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0124454.

@article{1336144,
   author = {Sovadinová, Iva and Babica, Pavel and Boke, Hatice and Kumar, Esha and Wilke, Andrew and Park, JoonandSuk and Trosko, James E. and Upham, Brad L.},
   article_location = {SAN FRANCISCO (USA)},
   article_number = {5},
   doi = {http://dx.doi.org/10.1371/journal.pone.0124454},
   keywords = {Phosphatidylcholine; PLC-Induced Dysregulation; Gap Junctions; Environmental Toxicants; Rat Liver; Cell Model},
   language = {eng},
   issn = {1932-6203},
   journal = {PLOS ONE},
   title = {Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model},
   url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124454#abstract0},
   volume = {10},
   year = {2015}
}

TY  - JOUR
ID  - 1336144
AU  - Sovadinová, Iva - Babica, Pavel - Boke, Hatice - Kumar, Esha - Wilke, Andrew - Park, Joon-Suk - Trosko, James E. - Upham, Brad L.
PY  - 2015
TI  - Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model
JF  - PLOS ONE
VL  - 10
IS  - 5
SP  - "nestránkováno"
EP  - "nestránkováno"
PB  - Public Library of Science
SN  - 19326203
KW  - Phosphatidylcholine
KW  - PLC-Induced Dysregulation
KW  - Gap Junctions
KW  - Environmental Toxicants
KW  - Rat Liver
KW  - Cell Model
UR  - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124454#abstract0
L2  - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124454#abstract0
N2  - Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants work through either signaling mechanisms or both. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways. In conclusion: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap junction channels are closed by toxicants vary. Thus, accurate assessments of risk posed by toxic agents, and the role of dietary phytochemicals play in preventing or reversing the effects of these agents must take into account the specific mechanisms involved in the cancer process.
ER  -

SOVADINOVÁ, Iva, Pavel BABICA, Hatice BOKE, Esha KUMAR, Andrew WILKE, Joon-Suk PARK, James E. TROSKO and Brad L. UPHAM. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model. \textit{PLOS ONE}. SAN FRANCISCO (USA): Public Library of Science, 2015, vol.~10, No~5, p.~''nestránkováno'', 16 pp. ISSN~1932-6203. Available from: https://dx.doi.org/10.1371/journal.pone.0124454.

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