Abstract
Objective To investigate the protective effect and mechanism of liquiritin (LIQ) on cardiomyocyte hypertrophy induced by angiotensin II (Ang II). Methods H9c2 cells were pretreated with LIQ before and after Ang II treatment. CCK8 assay was performed to evaluate cell viability. The cell surface area was measured by phalloidin staining. The mRNA expression of atrial and B-type natriuretic peptides (ANP and BNP, respectively) and β-myosin heavy chain (β-MHC) was determined by quantitative reverse transcription-polymerase chain reaction (RT-qPCR); the protein levels of arginyltransferase 1 (ATE1), transforming growth factor beta-activated kinase 1 (TAK1), phos-TAK1, c-Jun N-terminal kinases1/2 (JNK1/2), and phos-JNK1/2 were determined by Western blotting. After constructing the ATE1 overexpression cell models with the pcDNA3.1/ATE1, the abovementioned indicators were tested using the introduced methods. Results LIQ at a concentration of ≤30 μM was not cytotoxic to H9c2 cells before exposure to Ang II. The protective effect of LIQ was best observed at 30 μM after Ang II treatment. Phalloidin staining and RT-qPCR results indicated that the deposition of Ang II increased the cell surface area and levels of ANP, BNP, and β-MHC. On the other hand, Western blotting results showed that Ang II increased the ATE1 protein levels and TAK1 and JNK1/2 phosphorylation, which were significantly alleviated after LIQ treatment. LIQ also directly inhibited the ATE1 overexpression in H9c2 cells transfected with pcDNA3.1/ATE1 and further inhibited TAK1 and JNK1/2 phosphorylation. Conclusion LIQ can attenuate Ang II-induced cardiomyocyte hypertrophy by regulating the ATE1/TAK1-JNK1/2 pathway.
Highlights
Heart failure is a common life-threatening medical condition with high morbidity and mortality globally [1]
Licorice exhibits antihypertrophic activity, the antihypertrophic effect of its main component LIQ and the mechanism underlying the same remain unclear. erefore, we aimed to explore the antihypertrophic effects of LIQ on angiotensin II (Ang II)-induced cardiomyocyte hypertrophy and whether its possible underlying mechanism involves the arginyltransferase 1 (ATE1)/transforming growth factor beta-activated kinase 1 (TAK1)-Jun N-terminal kinases1/2 (JNK1/2) pathway
After LIQ treatment, the phosphorylation of TAK1 and JNK1/2 and ATE1 expression considerably reduced (P < 0.05, P < 0.01). These results demonstrate that LIQ could inhibit Ang II-induced cardiac hypertrophy by inhibiting the ATE1/TAK1-JNK1/2 pathway
Summary
Heart failure is a common life-threatening medical condition with high morbidity and mortality globally [1]. Cardiac hypertrophy, which is accompanied by increased cell death, fibrotic remodeling, and contractile dysfunction, is considered to play a pivotal role in the pathophysiological processes of heart failure [2, 3]. Inhibiting or delaying the progression of pathological cardiac hypertrophy can serve as an effective therapeutic strategy for preventing heart failure [4]. No effective drug is available to prevent or treat cardiac hypertrophy, and developing appropriate novel medications is crucial. Multiple signaling pathways are involved in cardiac hypertrophy development, among which ATE1 is an important target and acts as a regulator of hypertrophic response [7, 8]. A recent study showed that ATE1 regulates the expression of hypertrophic gene markers via the TAK1-JNK1/2 signaling pathway, which provides a potentially novel therapeutic target for treating cardiac hypertrophy [9]
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