Trichostatin a enhances gap junctional intercellular communication in primary cultures of adult rat hepatocytes.
The effects of histone deacetylase inhibitor Trichostatin A (TSA) on connexin (Cx) expression and gap junctional intercellular communication (GJIC) were investigated in primary cultures of adult rat hepatocytes. GJIC was monitored by using the scrape-loading/dye transfer method. Immunoblotting and immunocytochemistry were used to investigate Cx protein levels and localization. Cx gene expression was studied by means of quantitative reverse transcriptase-polymerase chain reaction. TSA increased Cx32 protein levels and affected negatively the Cx26 protein levels. The latter was preferentially located in the cytosol of cultured cells. TSA also promoted the appearance of Cx43 in the nuclear compartment of primary cultured hepatocytes. Overall, this resulted in enhanced GJIC activity. It is important to note that the time of onset of TSA treatment was crucial for the extent of its outcome and that the effects of TSA on Cx protein levels occurred independently of transcriptional changes. TSA differentially affects Cx proteins in primary rat hepatocyte cultures, suggesting distinct regulation and/or distinct roles of the different Cx species in the control of hepatic homeostasis. TSA enhances GJIC between primary cultured rat hepatocytes, an interesting finding supporting its use to further optimize liver-based in vitro models for pharmacotoxicological purposes.
Department of Toxicology, Vrije Universiteit Brussel, B-1090 Brussels, Belgium. mvinken@vub.ac.be
Mathieu
M
Vinken
Tom
T
Henkens
Tamara
T
Vanhaecke
Peggy
P
Papeleu
Albert
A
Geerts
Elke
E
Van Rossen
James Kevin
JK
Chipman
Paolo
P
Meda
Vera
V
Rogiers
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D017630:Connexins; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D012333:RNA, Messenger; C012589:trichostatin A; D007770:L-Lactate Dehydrogenase