G3BP2 is involved in isoproterenol-induced cardiac hypertrophy through activating the NF-κB signaling pathway

Abstract

The RasGAP SH3 domain-binding proteins (G3BPs) are a family of RNA-binding proteins that can co-ordinate signal transduction and post-transcriptional gene regulation. G3BPs have been shown to be involved in mediating a great diversity of cellular processes such as cell survival, growth, proliferation and apoptosis. But the potential roles of G3BPs in the pathogenesis and progression of cardiovascular diseases remain to be clarified. In the present study, we provide the first evidence that suggests the participation of G3BP2 in cardiac hypertrophy. In cultured neonatal rat cardiomyocytes (NRCMs), treatment with isoproterenol (ISO, 0.1-100 μmol/L) significantly elevated the mRNA and protein levels of G3BP2. Similar results were observed in the hearts of rats subjected to 7D-injection of ISO, accompanied by obvious heart hypertrophy and elevated the expression of hypertrophy marker genes ANF, BNP and β-MHC in heart tissues. Overexpression of G3BP2 in NRCMs led to hypertrophic responses evidenced by increased cellular surface area and the expression of hypertrophy marker genes, whereas knockdown of G3BP2 significantly attenuated ISO-induced hypertrophy of NRCMs. We further showed that G3BP2 directly interacted with IκBα and promoted the aggregation of the NF-κB subunit p65 in the nucleus and increased NF-κB-dependent transcriptional activity. NF-κB inhibition with PDTC (50 μmol/L) or p65 knockdown significantly decreased the hypertrophic responses in NRCMs induced by ISO or G3BP2 overexpression. These results give new insight into the functions of G3BP2 and may help further elucidate the molecular mechanisms underlying cardiac hypertrophy.

miR-139-5p inhibits isoproterenol-induced cardiac hypertrophy by targetting c-Jun

“…The activation of β-AR regulates cardiac excitation–contraction and leads to the increase in heart rate and cardiomyocyte contractility [ 21–23 ]. The hyperactivation of β-AR results in cardiac hypertrophy, fibrosis, senescence, inflammation, and cardiomyocyte apoptosis and necrosis [ 24–29 ]. The treatment of NRCMs with ISO caused cardiomyocyte enlargement and increased the expression of ANP and BNP.…”

Bakuchiol protects against pathological cardiac hypertrophy by blocking NF-κB signaling pathway

“…Some studies have revealed that NF-κB activation is required for the progression of cardiac hypertrophy. Recently, Hong et al [ 24 ] reported that NF-κB inhibition with PDTC or p65 knockdown significantly decreased the hypertrophic responses. Moreover, IKK/NF-κB activation in cardiomyocytes caused significant inflammatory cardiomyopathy and heart failure, while inhibition of the NF-κB signaling pathway by a nondegradable IκBα decreased cardiac hypertrophy and dysfunction induced by Ang II stimuli and pressure overload [ 25 ].…”

Rasputin a decade on and more promiscuous than ever? A review of G3BPs

“…Although the overexpression of G3BP1 alone is not enough to cause development of cardiac hypertrophy, it does have a role in the regulation of miR-1 during disease progression [67]. The potential role of G3BP2 in miRNA regulation in cardiac hypertrophy remains elusive, but it is involved in isoproterenolinduced cardiac hypertrophy by inducing the NFκB signalling pathway [68]. Interestingly, in situ hybridisation studies of G3BP2 mRNA in developing mouse embryos showed that its expression is reduced in the heart relative to other tissues (unpublished data by the author).…”