Abstract P082: Cardiac Calcium Handling and Protein Phosphatase 2A Activity Are Differentially Regulated by JNK1 and JNK2 MAP Kinases
| Autor: | Honey B Golden, Linley E Watson, Donald M Foster, David E Dostal |
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| Rok vydání: | 2011 |
| Předmět: | |
| Zdroj: | Circulation Research. 109 |
| ISSN: | 1524-4571 0009-7330 |
| DOI: | 10.1161/res.109.suppl_1.ap082 |
| Popis: | We previously identified the JNK-B56α-PP2A signaling axis as a major target in anthrax lethal toxin (LT)-induced cardiac dysfunction. Thus, we further tested whether LT-mediated loss in cardiac function is a consequence of dysregulated calcium handling resulting from JNK inactivation. To biochemically recapitulate the signaling effects of LT, we infected NRVM with HA-B56α adenovirus and determined PP2A activity as well as Ca 2+ i measurements. Over-expression of HA-B56α in NRVM did not induce a significant increase in cellular PP2A activity, however, it did induce a significant increase (p2+ i compared to virus control. Furthermore, PLB, PP2Ac and Akt protein co-immunoprecipitated with HA-B56α, and immunostaining revealed colocalization of B56α with PLB at the SR. Since B56α over-expression alone was not sufficient to induce PP2A activity or PP2A-mediated Ca 2+ i dysregulation, we hypothesized that JNK may serve as a functional regulator of Ca 2+ i handling through PP2A activation as well as B56α protein levels. Adenoviral-mediated over-expression of MEK7 in NRVM resulted in a significant reduction in LT-mediated Ca 2+ i dysregulation compared to virus control (p2+ i was significantly lost with knock-down of JNK1 compared to JNK2 (p2+ i levels (p2+ i dysregulation. Interestingly, immunoblotting of PLB did not reveal a JNK-dependent difference in PLB phosphorylation at Ser 16 , however, loss of JNK2 almost completely inhibited p-PLB-Thr 17 . Thus, our results suggest that JNK1 and JNK2 may differentially regulate Ca 2+ i through PP2A activation and PLB-Thr 17 phosphorylation, respectively. |
| Databáze: | OpenAIRE |
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