Differential Regulation of Phospholipase C-β Isozymes in Cardiomyocyte Hypertrophy

Frontier of Epilepsy Research - mTOR signaling pathway

“…PLC PLC (Phospholipase C) hydrolizes phosphatidylinositol-4, 5-bisphosphate (PIP 2 ) to produce inositol triphosphate (IP 3 ) and diacylgylcerol (DAG) which activate downstream signaling cascade including IP 3 receptors and PKC, respectively (Rhee, 2001). Among many isoforms, PLCβ3 has been shown to be upregulated by IGF-1 via PI3K and S6K, and PLCγ1-mediated activation of mTOR/S6K pathway (Schnabel et al, 2000;Markova et al, 2010). PLCβ1 null mice showed epilepsy, and age-dependent hippocampal mossy fiber sprouting (Kim et al, 1997;Böhm et al, 2002).…”

Losartan attenuates phospholipase C isozyme gene expression in hypertrophied hearts due to volume overload

“…An early increase in angiotensinogen mRNA levels as well as that Ang II is the first growth factor produced in volume overloaded hearts has been reported [35]. In addition, both growth hormone and insulin-like growth factor-1 (IGF-1) both have been shown to induce a substantial increase in PLC β 3 mRNA expression [15]. Interestingly, growth hormone and IGF-1 are both increased in the volume overloaded heart [35,36] and therefore may also be involved in the increased expression of PLC β isozymes seen in the present study.…”

“…Although cardiac hypertrophy may initially be a beneficial response, it can also be viewed as a stepping-stone or precursor to the development of heart failure [17,[23][24][25][26]. In the myocardium, PLC is considered to play a role in the development of myocardial hypertrophy [15,17]. In fact, we have previously demonstrated that inhibition of PLC activities with U73122 attenuates norepinephrineinduced increases in atrial natriuretic factor gene expression and protein synthesis in isolated adult rat cardiomyocytes [16].…”

“…Interestingly, growth hormone and IGF-1 are both increased in the volume overloaded heart [35,36] and therefore may also be involved in the increased expression of PLC β isozymes seen in the present study. Because PLC is documented to play a role in cardiac hypertrophy [11][12][13][14][15][16][17], this study has shown that the chamber specific and time-dependent increases in PLC isozyme gene expression may be part of the amplification of the PLC mediated signal transduction processes involved in cardiac hypertrophy. It should be noted that the regression of cardiac hypertrophy in experimental animals may indicate a causal relationship between PLC function and losartan therapy.…”

“…In other studies the development of cardiac concentric hypertrophy in stroke-prone spontaneously hypertensive rats, was observed to involve an increase in the PLC signaling pathway [12,13]. Also, the activation of PLC has been shown to be associated with the hypertrophic response of isolated cardiomyocytes exposed to different agents [14][15][16]. In an earlier study, we have reported an increase in PLC isozyme gene and protein expression as well as activities in the hypertrophied left ventricle (LV), due to volume overload induced by an arteriovenous (AV) shunt in the rat [17].…”