Abstract：
:PICOT (PKC-interacting cousin of thioredoxin) was previously shown to inhibit the development of cardiac hypertrophy, concomitant with an increase in cardiomyocyte contractility. To explore the physiological function of PICOT in the hearts, we generated a PICOT-deficient mouse line by using a gene trap approach. PICOT(-/-) mice were embryonic lethal indicating that PICOT plays an essential role during embryogenesis, whereas PICOT(+/-) mice were viable with no apparent morphological defects. The PICOT protein levels were reduced by about 50% in the hearts of PICOT(+/-) mice. Significantly exacerbated cardiac hypertrophy was induced by pressure overload in PICOT(+/-) mice relative to that seen in wild type littermates. In line with this observation, calcineurin-NFAT signaling was greatly enhanced by pressure overload in the hearts of PICOT(+/-) mice. Cardiomyocytes from PICOT(+/-) mice exhibited significantly reduced contractility, which may be due in part to hypophosphorylation of phospholamban and reduced SERCA activity. These data indicate that the precise PICOT protein level significantly affects the process of cardiac hypertrophy and cardiomyocyte contractility. We suggest that PICOT plays as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Cha H,Kim JM,Oh JG,Jeong MH,Park CS,Park J,Jeong HJ,Park BK,Lee YH,Jeong D,Yang DK,Bernecker OY,Kim DH,Hajjar RJ,Park WJdoi
10.1016/j.yjmcc.2008.09.124subject
Has Abstractpub_date
2008-12-01 00:00:00pages
796-803issue
6eissn
0022-2828issn
1095-8584pii
S0022-2828(08)00585-3journal_volume
45pub_type
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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journal_title：Journal of molecular and cellular cardiology
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doi：10.1006/jmcc.1993.1157
更新日期：1993-12-01 00:00:00
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journal_title：Journal of molecular and cellular cardiology
pub_type： 杂志文章
doi：10.1006/jmcc.1996.0226
更新日期：1996-12-01 00:00:00
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