Chih-Ying Changchien
Republic of China Air Force, Taiwan
Title: Indoxyl sulfate(IS) suppressed myocardial connexin43(Cx43) translation and phosphorylation via JNK activation
Biography
Biography: Chih-Ying Changchien
Abstract
Heart rhythm disturbances has been widely recognized as major trigger of cardiovascular (CV) mortality in chronic kidney disease (CKD) patients. Connexin43 (Cx43)-composed gap junctions are essential in cardiomyocytes synchronization and may involve in pathological response to uremic toxins. In primary culture of rat neonatal cardiomyocytes, we demonstrated that indoxyl sulfate (IS) treatment decreased spontaneous contractions without viability impairment. Meanwhile, there was disruption of gap junction intercellular communication (GJIC) between cardiomyocytes since 30 minutes of IS stimulation. This phenomenon implicated close association between ISinduced bradycardia and gap junction alterations. Effect of IS caused time- and dose- dependent Cx43 redistribution. The patterns of Cx43 immunostaining returned to baseline when IS stimulation diminished. Furthermore, showterm IS exposure downregulated Cx43 total protein, phosphorylated form and mRNA level. The above changes as well as GIJC and Cx43 suppression were reversed by pretreatment with JNK inhibitor (SP600125). Elevated JNK1 and JNK2 phosphorylation were further identified post IS exposure 15 minutes. The inhibition of p-JNK could attenuate IS-mediated downward trends in Cx43 transcription and translation. Our findings disclose that IS might remodel myocardial gap junction and Cx43 expression through JNK regulation.