Article

Regulation of connexin expression by transcription factors and epigenetic mechanisms.

Department of Food Science and Human Nutrition, Faculty of Human Life Sciences, Fuji Women's University, Ishikarishi, Japan.
Biochimica et Biophysica Acta (impact factor: 4.66). 01/2012; DOI:10.1016/j.bbamem.2011.12.031
Source: PubMed

ABSTRACT Gap junctions are specialized cell-cell junctions that directly link the cytoplasm of neighboring cells. They mediate the direct transfer of metabolites and ions from one cell to another. Discoveries of human genetic disorders due to mutations in gap junction protein (connexin [Cx]) genes and experimental data on connexin knockout mice provide direct evidence that gap junctional intercellular communication is essential for tissue functions and organ development, and that its dysfunction causes diseases. Connexin-related signaling also involves extracellular signaling (hemichannels) and non-channel intracellular signaling. Thus far, 21 human genes and 20 mouse genes for connexins have been identified. Each connexin shows tissue- or cell-type-specific expression, and most organs and many cell types express more than one connexin. Connexin expression can be regulated at many of the steps in the pathway from DNA to RNA to protein. In recent years, it has become clear that epigenetic processes are also essentially involved in connexin gene expression. In this review, we summarize recent knowledge on regulation of connexin expression by transcription factors and epigenetic mechanisms including histone modifications, DNA methylation, and microRNA. This article is part of a Special Issue entitled: The communicating junctions, roles and dysfunctions (Pt II).

0 0
 · 
1 Bookmark
 · 
50 Views
  • Source
    Article: Deciphering the potential efficacy of acetyl-L-carnitine (ALCAR) in maintaining connexin-mediated lenticular homeostasis.
    Arumugam Ramachandran Muralidharan, George Leema, Thangaraj Annadurai, Thirugnanasambandhar Sivasubramanian Anitha, Philip A Thomas, Pitchairaj Geraldine
    [show abstract] [hide abstract]
    ABSTRACT: To determine the putative role of acetyl-L-carnitine (ALCAR) in maintaining normal intercellular communication in the lens through connexin. In the present study, Wistar rat pups were divided into 3 groups of eight each. On postpartum day ten, Group I rat pups received an intraperitoneal injection (50 µl) of 0.89% saline. Rats in Groups II and III received a subcutaneous injection (50 µl) of sodium selenite (19 µmol/kg bodyweight); Group III rat pups also received an intraperitoneal injection of ALCAR (200 mg/kg bodyweight) once daily on postpartum days 9-14. Both eyes of each pup were examined from day 16 up to postpartum day 30. Alterations in the mean activity of the channel pumps, calcium-ATPase and sodium/potassium-ATPase, were determined. The expression of genes encoding key lenticular gap junctions (connexin 46 and connexin 50) and a channel pump (plasma membrane Ca(2+)-ATPase [PMCA1]) was evaluated by reverse transcription-PCR. Immunoblot analysis was also performed to confirm the differential expression of key lenticular connexin proteins. In addition, bioinformatics analysis was performed to determine the interacting residues of the connexin proteins with ALCAR. Significantly lower mean activities of Ca(2+)-ATPase and Na(+)/K(+) -ATPase were observed in the lenses of Group II rats than those in Group I rat lenses. However, the observed mean activities of Ca(2+)-ATPase and Na(+)/K(+)-ATPase in Group III rat lenses were significantly higher than those in Group II rat lenses. The mean mRNA transcript levels of the connexin 46 and connexin 50 genes were significantly lower, while the mean levels of PMCA1 gene transcripts were significantly higher, in Group II rat lenses than in Group I rat lenses. Immunoblot analysis also confirmed the altered expression of connexin proteins in lysates of whole lenses of Group II rats. However, the expression of connexin 46 and connexin 50 proteins in lenses from group III rats was essentially similar to that noted in lenses from normal (Group I) rats. Hydrogen bond-interaction between ALCAR and amino acid residues at the functional domain regions of connexin 46 and connexin 50 proteins was also demonstrated through bioinformatics tools. The results suggest that ALCAR plays a key role in maintaining lenticular homeostasis by promoting gap junctional intercellular communication.
    Molecular vision 01/2012; 18:2076-86. · 2.20 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

20 mouse genes
 
21 human genes
 
cell types
 
communicating junctions
 
connexin knockout mice
 
direct transfer
 
DNA methylation
 
dysfunction causes diseases
 
dysfunctions
 
epigenetic mechanisms
 
epigenetic processes
 
gap junction protein
 
gap junctional intercellular communication
 
Gap junctions
 
histone modifications
 
human genetic disorders
 
non-channel intracellular signaling
 
Pt II
 
Special Issue
 
tissue functions
 

Masahito Oyamada