PKA rapidly enhances proteasome assembly and activity in in vivo XXXX hearts.

@entity63 @entity235 @entity1188 @entity2975 @entity6395 @entity3044 @entity9501 @entity1928
Proteasome regulates diverse cellular functions by eliminating ubiquitinated proteins. Protein kinase A (PKA) is a key regulator of proteasome activity. However, it remains unknown how PKA regulates proteasome activity and whether it controls proteasome activity in in vivo hearts. Both the in vitro peptidase assay and the in-gel peptidase assays showed that the treatment with PKA for 30 min dose-dependently activated purified 26S proteasome. Simultaneously, PKA treatment enhanced phosphorylation and assembly of purified 26S proteasome evaluated by non-reducing native @entity2975 gel electrophoresis, either of which was blunted by the pretreatment with a PKA inhibitor, @entity9501 . In in vivo @entity235 hearts, proteasome assembly and activity were enhanced 30 min after the exogenous or endogenous stimulation of PKA by the intracoronary administration of @entity3044 or @entity1928 for 30 min or by @entity63 ( @entity63 ) with 4 times of repeated 5 min of @entity63 . The intracoronary administration of @entity9501 blunted the enhancement of proteasome assembly and activity by @entity63 . Myocardial proteasome activity at the end of @entity63 was decreased compared with the control, however, it did not differ from the control in @entity235 with @entity63 . @entity63 decreased the accumulation of ubiquitinated proteins in the @entity235 @entity63 /reperfusion myocardium, which was blunted by the intracoronary administration of a proteasome inhibitor, @entity6395 . However, proteasome activation by @entity63 was not involved in its @entity1188 size-limiting effects. These findings indicate that PKA rapidly enhances proteasome assembly and activity in in vivo hearts. Further investigation will be needed to clarify pathophysiological roles of PKA-mediated proteasome activation in @entity63 /reperfusion hearts.
