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Ins(1,4,5)P(3) regulates phospholipase Cbeta1 expression in cardiomyocytes
Oliver Vasilevski1, David R Grubb, Theresa M Filtz
1Cellular Biochemistry Laboratory, Baker Heart Research Institute, 75 Commercial Road, Melbourne, 3004, Victoria, Australia.
Journal of Molecular and Cellular Cardiology
|August 12, 2008
Summary
The study reveals that inositol(1,4,5)trisphosphate (IP(3)) levels in the heart are regulated by a feedback loop involving phospholipase C beta 1 (PLCbeta1). This suggests a crucial, previously debated, functional role for IP(3) signaling in cardiac cells.
Area of Science:
- Cardiovascular Biology
- Cell Signaling
- Molecular Cardiology
Background:
- The role of inositol(1,4,5)trisphosphate (IP(3)), a calcium-releasing second messenger, in cardiac function remains debated.
- IP(3) is generated from phosphatidylinositol(4,5)bisphosphate (PIP(2)) and influences cardiac effectors.
Purpose of the Study:
- To investigate the functional significance of IP(3) in cardiomyocytes.
- To elucidate the regulatory mechanisms controlling IP(3) levels within cardiac cells.
Main Methods:
- Overexpression of IP(3) 5-phosphatase in neonatal rat ventricular myocytes (NRVM) to enhance IP(3) degradation.
- Assessment of phospholipase C (PLC) activity and expression of PLC isoforms.
- Utilizing IP(3)-receptor (type 2) knockout mouse hearts.
Main Results:
- Acute overexpression of IP(3) 5-phosphatase reduced IP(3) signaling, but chronic stimulation led to increased PLC activity and selective upregulation of PLCbeta1 expression, normalizing IP(3) levels.
- Sequestration of IP(3) also increased PLC activity and PLCbeta1 expression, indicating IP(3) availability regulates PLCbeta1.
- IP(3)-receptor (type 2) knockout hearts exhibited elevated PLCbeta1 expression.
Conclusions:
- Inositol(1,4,5)trisphosphate and IP(3)-receptor (type 2) signaling form a regulatory loop that controls PLCbeta1 expression.
- This feedback mechanism maintains cellular IP(3) levels, implying a significant functional role for IP(3) in the heart.
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