Stimulation of 42/44kDa mitogen-activated protein kinases by arginine vasopressin in rat cardiomyocytes

Abstract

Vasoconstrictors, such as angiotensin II (Ang II), are involved in the regulatory mechanisms of post myocardial infarction (MI) hypertrophy. Arginine vasopressin (AVP), may be another vasoconstrictor that influences the mechanisms that lead to post MI hypertrophy. In these studies we investigated the possible activation of the 42/44 kDa mitogen-activated protein kinases (MAPKs), also referred as extracellular signal regulated kinases (ERKs), in cultured cardiomyocytes. Treatment of rat cardiomyocytes with AVP, Ang II and phorbol 12-myristate 13-acetate (PMA) increases the activation of ERKs. The activity of the 42/44 kDa MAPKs was tested using the phosphorylation of: (1) EGF receptor peptide (EGFR-P); (2) myelin basic protein (MBP) immobilized in poly acrylamide gels; and (3) T183 and Y185 residues of these proteins. The activity of the MAPKs, induced by AVP or PMA was inhibited by downregulation of protein kinase C (PKC), by the tyrosine kinase inhibitor genistein and by MAPK kinase (MEK) inhibitor, PD98059. In addition, the AVP-induced stimulation of MAPKs was shown to be mediated through a V1 receptor. We suggest that AVP activates the 42/44kDa MAPKs through a signal transduction pathway that involves stimulation of AVP-V1 receptor, tyrosine kinase, PKC and MEK. These results suggest that AVP may be involved in ERKs dependent regulatory functions of cardiomyocytes growth.

Bioengineered Cardiac Grafts : A New Approach to Repair the Infarcted Myocardium?

“…5 Briefly, female Sprague-Dawley rats that were carrying 16-day-old embryos were operated on while they were under deep anesthesia. The embryos were removed, and their hearts were placed in cold dissociation buffer.…”

Mitogen-activated protein kinases in the heart

“…Stimulation of many receptor classes can activate ERK including receptors with intrinsic tyrosine kinase activity, cytokine receptors and GPCR, including those coupling via G-proteins of the G q/11 , the G i/o and the G s family (Widmann et al 1999). In the heart, ERK stimulation has been 247 Raf-1, c-Raf, c-Raf-1 Mos - Tak1 -MUK DLK, ZPK SPRK PTK-1, MLK-3 MST MLK2 MEKK1 -MEKK2 -MEKK3 -MEKK4 MTK1 Tpl-2 Cot, Est ASK1 MAPKKK5 shown by acidic fibroblast growth factor, insulin-like growth factor-I, estrogen, neuregulin-1, antrial natriuretic peptide (ANP), α 1 -adrenoceptor agonists, β-adrenoceptor agonists, muscarinic receptor agonists, adenosine, endothelin-1 and -3, angiotensin II, neuropeptide Y, prostaglandin F 2α , bradykinin, arginine vasopressin, lysophosphatidic acid, the cardiotoxic agent daunomycin and, cGMP-independently, by nitroprusside (Adams et al 1998a;Aharonovitz et al 1998;Baliga et al 1999;Bogoyevitch and Sugden 1996;Clerk et al 1996;Communal et al 2000;Foncea et al 1997;Haq et al 1998;Kim et al 2000;Lavandero et al 1998;Nuedling et al 1999;Page and Doubell 1996;Pellieux et al 2000;Silberbach et al 1999;Takemoto et al 1999;Xu et al 2000;Zhu et al 1999; Table 3). Moreover, cardiac ERK can be activated receptorindependently by PKC-activating phorbol esters, elevation of intracellular cGMP content or the Na + /K + -ATPase inhibitor ouabain and by complex stimuli such as foetal calf serum, mechanical stretch, H 2 O 2 and osmotic shock (Aikawa et al 1997;Andersson et al 1998;Bogoyevitch and Sugden 1996;Knight and Buxton 1996;…”

“…An alternative pathway of ERK stimulation by G q/11 -coupled receptors may involve PKC activation. For example ERK activation by α 1 -adrenoceptor agonists, angiotensin II, endothelin-1, bradykinin (via B 2 receptors), arginine vasopressin (via V 1 receptors) or lysophosphatidic acid has been shown to be PKC-dependent in rat cardiomyocytes (Aharonovitz et al 1998;Bogoyevitch and Sugden 1996;Clerk et al 1996;Xu et al 2000;Yamazaki et al 1995Yamazaki et al , 1999Zou et al 1996). However, in some studies α 1 -adrenoceptor-stimulated ERK activation was not prevented by PKC inhibitors (Snabaitis et al 2000).…”

Regulated expression of GRP78 during vasopressin‐induced hypertrophy of heart‐derived myocytes

“…The subsequent stimulation of protein synthesis, in contrast, is unaffected by changes in extracellular Ca 2 , depends on gene transcription, is suppressed by a protein kinase C (PKC) pseudosubstrate sequence, and is observed at pM vasopressin concentrations. H9c2 myocytes, like neonatal cardiomyocytes [van der Bent et al, 1994;Aharonovitz et al, 1998;Liu et al, 1999;Xu et al, 1999Xu et al, , 2000] and adult hearts [Fukuzawa et al, 1999;Nakamura et al, 2000], possess all basic features of V1-vasopressin signaling [Tran et al, 1995;Reilly et al, 1998;Chen and Chen, 1999] and undergo hypertrophy in response to the hormone [Brostrom et al, 2000]. Hypertrophy occurs at pM vasopressin concentrations, depends on PKC activity, and precedes full repletion of Ca 2 stores.…”