Abstract:
:Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACβ > PP2ACα > PP4C > PP6C), NRVM (PP2ACβ > PP2ACα = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACα > PP2ACβ > PP6C > PP4C). Western analysis confirmed that all type 2A catalytic subunits were expressed in H9c2 cardiomyocytes; however, PP4C protein was absent in adult myocytes and only detectable following 26S proteasome inhibition. Short-term knockdown of alpha4 protein expression attenuated expression of all type 2A catalytic subunits. Pressure overload-induced left ventricular (LV) hypertrophy was associated with an increase in both PP2AC and alpha4 protein expression. Although PP6C expression was unchanged, expression of PP6C regulatory subunits (1) Sit4-associated protein 1 (SAP1) and (2) ankyrin repeat domain (ANKRD) 28 and 44 proteins was elevated, whereas SAP2 expression was reduced in hypertrophied LV tissue. Co-immunoprecipitation studies demonstrated that the interaction between alpha4 and PP2AC or PP6C subunits was either unchanged or reduced in hypertrophied LV tissue, respectively. Phosphorylation status of phospholemman (Ser63 and Ser68) was significantly increased by knockdown of PP2ACα, PP2ACβ, or PP4C protein expression. DNA damage assessed by histone H2A.X phosphorylation (γH2A.X) in hypertrophied tissue remained unchanged. However, exposure of cardiomyocytes to H2O2 increased levels of γH2A.X which was unaffected by knockdown of PP6C expression, but was abolished by the short-term knockdown of alpha4 expression. This study illustrates the significance and altered activity of the type 2A protein phosphatase-alpha4 complex in healthy and hypertrophied myocardium.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Eleftheriadou O,Boguslavskyi A,Longman MR,Cowan J,Francois A,Heads RJ,Wadzinski BE,Ryan A,Shattock MJ,Snabaitis AKdoi
10.1007/s00395-017-0625-2subject
Has Abstractpub_date
2017-07-01 00:00:00pages
37issue
4eissn
0300-8428issn
1435-1803pii
10.1007/s00395-017-0625-2journal_volume
112pub_type
杂志文章abstract::The antiarrhythmic effect of carbocromene (Intensain) was studied in 17 anaesthetized dogs. Ventricular tachycardia was induced by infusion of K-strophanthin (mean dose: 154 mug/kg i.v.). In 25 out of 26 experiments carbocromene (4 mg/kg i.v.) was effective. Ventricular tachycardia was converted to sinus rhythm in 16 ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01914339
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907920
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journal_title:Basic research in cardiology
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907648
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journal_title:Basic research in cardiology
pub_type: 杂志文章
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-016-0541-x
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906520
更新日期:1978-07-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908180
更新日期:1985-07-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
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更新日期:1985-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
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pub_type: 杂志文章,评审
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/978-3-642-72376-6_2
更新日期:1984-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF02005340
更新日期:1982-07-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906369
更新日期:1977-03-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950050096
更新日期:1998-08-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1985-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907942
更新日期:1982-09-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907365
更新日期:1988-05-01 00:00:00
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journal_title:Basic research in cardiology
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journal_title:Basic research in cardiology
pub_type: 杂志文章
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journal_title:Basic research in cardiology
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907360
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950050145
更新日期:1999-06-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1975-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906463
更新日期:1983-09-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950200053
更新日期:2002-11-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00795058
更新日期:1992-09-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950200049
更新日期:2002-09-01 00:00:00