Phospholipase C gene expression, protein content, and activities in cardiac hypertrophy and heart failure due to volume overload

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 287; no. 2; pp. H719 - H727
• Main Authors: Dent, Melissa R, Dhalla, Naranjan S, Tappia, Paramjit S
• Format: Journal Article
• Language: English
• Published: United States 01.08.2004
• Subjects: Animals; Cardiac Output, Low - enzymology; Cardiac Output, Low - etiology; Cardiac Output, Low - physiopathology; Cardiomegaly - enzymology; Cardiomegaly - physiopathology; Cytosol - metabolism; Diglycerides - metabolism; Gene Expression; Hyperemia - complications; Inositol 1,4,5-Trisphosphate - metabolism; Isoenzymes - genetics; Isoenzymes - metabolism; Male; Phosphatidylinositol 4,5-Diphosphate - metabolism; Rats; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Sarcolemma - metabolism; Type C Phospholipases - genetics; Type C Phospholipases - metabolism; Ventricular Function, Left
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.01107.2003

1 Department of Physiology, Faculty of Medicine; and 2 Department of Human Nutritional Sciences, Faculty of Human Ecology, Institute of Cardiovascular Sciences, St. Boniface Hospital Research Centre University of Manitoba, Winnipeg, Manitoba R2H 2A6, Canada Submitted 24 November 2003 ; accepted in final form 8 March 2004 Volume overload due to arteriovenous (AV) shunt results in cardiac hypertrophy followed by the progression to heart failure. The phosphoinositide phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP 2 ) to 1,2-diacylglycerol (DAG) and inositol (1,4,5)-trisphosphate (IP 3 ), which are known to influence cardiac function. Therefore, we examined the time course of changes in DAG and IP 3 as well as PLC isozyme gene expression, protein content, and activities in cardiac hypertrophy and heart failure induced by AV shunt in Sprague-Dawley rats by the needle technique. An increase in the left ventricle (LV)-to-body weight ratio demonstrated that LV hypertrophy was established at 4 wk after the induction of the shunt. PLC- 1 activity was increased two- and sevenfold at 3 days and 1 and 2 wk after the induction of volume overload, respectively. These changes were associated with increases in the mRNA and sarcolemmal (SL) protein content; however, no changes in PLC- 1 were detected at 4 wk. On the other hand, a significant increase in PLC- 1 activity as well as mRNA and SL protein was seen at 3 days and 4 wk. A progressive decrease in PLC- 1 activity with concomitant reductions in the gene expression and SL protein abundance was detected during 1 to 4 wk. Activity of 1 - and 1 -isozymes was significantly depressed during the 8- and 16-wk time points, whereas 1 -isozyme was increased significantly during these time points. A progressive decrease in the SL PIP 2 content was observed during cardiac hypertrophy and heart failure. Our findings indicate that PLC isozyme signaling processes are increased in hypertrophy and decreased in heart failure due to volume overload. cardiac sarcolemma; signal transduction Address for reprint requests and other correspondence: P. S. Tappia, Institute of Cardiovascular Sciences, Laboratory of Cardiac Membrane Biology, St. Boniface General Hospital Research Centre (R3020), 351 Tache Ave., Winnipeg, Manitoba R2H 2A6, Canada (E-mail: ptappia{at}sbrc.ca ).