The muscle-CAT (M-CAT) promoter element is found on promoters of most 
muscle-specific cardiac genes, but its role in cardiac pathology is poorly 
understood. Here we studied whether the M-CAT element is involved in 
hypertrophic process activated by mechanical stretch, and identified the 
intracellular pathways mediating the response. When an in vitro stretch model of 
cultured neonatal rat cardiomyocytes and luciferase reporter construct driven by 
rat B-type natriuretic peptide (BNP) promoter were used, mutation of M-CAT 
element inhibited not only the basal reporter activity (88%), but also the 
stretch-activated BNP transcription (58%, p < 0.001). Stretch-induced BNP 
promoter activation was associated with an increase in transcriptional enhancer 
factor-1 (TEF-1) binding activity after 24 h mechanical stretch (p < 0.05). 
Inhibition of mitogen-activated protein kinases ERK, JNK, or p38 attenuated 
stretch-induced BNP activation. Interestingly, as opposed to p38 and JNK, 
inhibition of ERK had no additional effect on transcriptional activity of BNP 
promoter harboring the M-CAT mutation, suggesting a pivotal role for ERK in 
regulating stretch-induced BNP transcription via M-CAT binding site. Finally, 
immunoprecipitation studies showed that mechanical stretch induced myocyte 
enhancer factor-2 (MEF-2) binding to TEF-1. These data suggest a central role 
for M-CAT element in regulation of mechanical stretch-induced hypertrophic 
response via ERK activation.