INTRODUCTION AND METHODS: The effects of long-term β-adrenergic administration on the expression levels of the cardiac L-type Ca channel β2 subunit, which regulates channel trafficking and function, were characterized in adult rats. RESULTS: Systemic administration of isoproterenol (150 mg·kg·h) for 2 d led to a 50% increase in the ventricular wet weight-to-body weight ratio (mg/g) and of more than two-fold in the expression of actin protein. In contrast, β2 subunit protein levels decreased (down to 49%), while mRNA levels remained unchanged. Furthermore, levels of microRNAs (miRs), including miR-21 and miR-132, were upregulated (7.2 and 7.9 fold, respectively). Transfection of these miRs into HEK293 cells attenuated expression of a luciferase reporter gene controlled by a conserved 3'-untranslated region (UTR) of the β2 subunit (down to 67% and 56%, respectively). Systemic administration of isoproterenol also led to briefer intracellular Ca transients during action potentials measured in isolated cardiomyocytes (down to 65%). CONCLUSION: These results suggest that cardiac L-type Ca channel β2 subunit protein expression may be downregulated by miRs in response to long-term activation of β-adrenergic signaling, possibly as an adaptive response in cardiac hypertrophy and sustained β-adrenergic states.
INTRODUCTION AND METHODS: The effects of long-term β-adrenergic administration on the expression levels of the cardiac L-type Ca channel β2 subunit, which regulates channel trafficking and function, were characterized in adult rats. RESULTS: Systemic administration of isoproterenol (150 mg·kg·h) for 2 d led to a 50% increase in the ventricular wet weight-to-body weight ratio (mg/g) and of more than two-fold in the expression of actin protein. In contrast, β2 subunit protein levels decreased (down to 49%), while mRNA levels remained unchanged. Furthermore, levels of microRNAs (miRs), including miR-21 and miR-132, were upregulated (7.2 and 7.9 fold, respectively). Transfection of these miRs into HEK293 cells attenuated expression of a luciferase reporter gene controlled by a conserved 3'-untranslated region (UTR) of the β2 subunit (down to 67% and 56%, respectively). Systemic administration of isoproterenol also led to briefer intracellular Ca transients during action potentials measured in isolated cardiomyocytes (down to 65%). CONCLUSION: These results suggest that cardiac L-type Ca channel β2 subunit protein expression may be downregulated by miRs in response to long-term activation of β-adrenergic signaling, possibly as an adaptive response in cardiac hypertrophy and sustained β-adrenergic states.
Authors: Nicole R Parker; Nelson Correia; Brendan Crossley; Michael E Buckland; Viive M Howell; Helen R Wheeler Journal: Transl Oncol Date: 2013-12-01 Impact factor: 4.243
Authors: Il-Man Kim; Yongchao Wang; Kyoung-Mi Park; Yaoping Tang; Jian-Peng Teoh; Joseph Vinson; Christopher J Traynham; Gianluigi Pironti; Lan Mao; Huabo Su; John A Johnson; Walter J Koch; Howard A Rockman Journal: Circ Res Date: 2013-12-13 Impact factor: 17.367
Authors: Richard D Bagnall; Tatiana Tsoutsman; Rhian E Shephard; William Ritchie; Christopher Semsarian Journal: PLoS One Date: 2012-09-14 Impact factor: 3.240
Authors: Mary K McGahon; Janet M Yarham; Aideen Daly; Jasenka Guduric-Fuchs; Lyndsey J Ferguson; David A Simpson; Anthony Collins Journal: PLoS One Date: 2013-06-14 Impact factor: 3.240