In conclusion, Vandetanib we demonstrated that treatment with dobutamine in neonatal rat cardiomyocytes can increase PPAR�� expression by an activation of the ��1-adrenoceptor through cAMP to activate PKA and increase intracellular calcium levels. This increase may induce calmodulin and calcineurin activation which could result in higher PPAR�� protein expression. Taken together, increases in PPAR�� protein expression and cTnI phosphorylation are responsible for dobutamine-induced cardiac action, suggesting a new mechanism for dobutamine-induced cardiac contraction.Author’s ContributionThe first two authors contributed equally to this work (M. T. Chou & S. H. Lo).
AbbreviationsPPAR��:Peroxisome proliferator-activated receptors ��cTnI:Cardiac troponin IATP:Adenosine triphosphatecAMP:Cyclic adenosine monophosphateTnI:Troponin ICn:CalcineurinCaMK:Calcium/calmodulin-dependent protein kinasePPARs:Peroxisome proliferator-activated receptorsDMEM:Dulbecco/Vogt modified Eagle’s minimal essential mediumFBS:Foetal bovine serumRIPA:Radio-immuno-precipitation assayBAPTA:BAPTA-AMIBMX:3-isobutyl-1-methylxanthinePKA:Protein kinase APKAI:Inhibitor of protein kinase ACsA:Cyclosporine A.
Dengue is a noncontagious infectious disease caused by dengue virus (DENV), which is a positive-sense, single-stranded RNA virus that belongs to the family Flaviviridae, genus Flavivirus. DENV is classified into four antigenically distinct serotypes: DENV-1, DENV-2, DENV-3, and DENV-4 [1�C3]. The number of nations and people affected has increased steadily and today is considered the most widely spread arbovirus (arthropod-borne viral disease) in the world.
An estimated 50 million dengue infections occur annually and approximately 2.5 billion people live in dengue endemic countries [4]. Dengue can be presented in three main clinical forms: undifferentiated febrile illness, dengue fever (DF), and dengue AV-951 hemorrhagic fever (DHF) with or without shock syndrome known as dengue shock syndrome (DSS). The DF is presented as a self-limiting acute febrile illness that lasts for about 4 to 5 days. The disease begins abruptly with high fever, retroorbital pain, headaches of varying degrees, maculopapular rash, muscle and joint aches, and can also be observed mild hemorrhagic phenomena. In DHF/DSS, in addition to the initial symptoms corresponding to DF, between the second and fourth days of infection, there is an increased thrombocytopenia and bleeding phenomena, abdominal pain, and leakage of fluid into the interstitium, which can lead to decrease intravascular plasma volume and consequent hypovolemic shock that in some cases could be fatal [5]. The absence of an appropriate animal model for studying the disease has hindered the understanding of dengue pathogenesis.