title: Myocardial connexin-43 and PKC signalling are involved in adaptation of the heart to irradiation-induced injury: Implication of miR-1 and miR-21.
abstract: Intercellular connexin-43 (Cx43) channels are essential for electrical coupling and direct cardiac cell to cell communication to ensure heart function. Expression of Cx43 is altered due to stressful conditions and also affected by the alterations in extracellular matrix. We aimed to explore the effect of chest irradiation on myocardial expression of Cx43 and miR-1 which regulates GJA1 gene transcription for Cx43. Implication of miR-21 that regulates expression of extracellular matrix proteins and PKC signalling that may affect Cx43-mediated coupling was examined as well. Western blot and real-time PCR analyses revealed that six weeks after the exposure of healthy Wistar rats chest to single irradiation of 25 Gy significant myocardial alterations were observed: 1)/ increase of total Cx43 protein expression and its functional phosphorylated forms; 2) suppressed levels of miR-1; 3) enhanced expression of PKCε which phosphorylates Cx43; 4) increase of miR-21 levels; 5) increase of PKCδ expression. These results suggest that irradiation causes post-transcriptional regulation of myocardial Cx43 expression by miR-1 possibly through miR-21 and PKC signalling. We conclude that single dose of irradiation has the potential to enhance myocardial intercellular communication that might be beneficial for the heart that needs to be investigated in details in further studies.
authors.affiliation: Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic. narcisa.tribulova@savba.sk.
authors.forename: Csilla
authors.initials: C
authors.lastname: Viczenczova
authors.forename: Barbara
authors.initials: B
authors.lastname: Szeiffova Bacova
authors.forename: Tamara
authors.initials: T
authors.lastname: Egan Benova
authors.forename: Branislav
authors.initials: B
authors.lastname: Kura
authors.forename: Chang
authors.initials: C
authors.lastname: Yin
authors.forename: Peter
authors.initials: P
authors.lastname: Weismann
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kukreja
authors.forename: Jan
authors.initials: J
authors.lastname: Slezak
authors.forename: Narcis
authors.initials: N
authors.lastname: Tribulova
mesh_terms: D000222:Adaptation, Physiological / Q000528:radiation effects; D000818:Animals; D018031:Connexin 43 / Q000378:metabolism*; D006321:Heart / Q000528:radiation effects; D006335:Heart Injuries / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D011832:Radiation Injuries / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D018031:Connexin 43; C580592:Gja1 protein, rat; C542191:MIRN1 microRNA, rat; D035683:MicroRNAs; C546082:mirn21 microRNA, rat; D011493:Protein Kinase C