title: Tetramethylpyrazine inhibits angiotensin II-induced cardiomyocyte hypertrophy and tumor necrosis factor-α secretion through an NF-κB-dependent mechanism.
abstract: Tetramethylpyrazine (TMP), a bioactive compound isolated from the Chinese herb, Ligusticum wallichii Franchat, has been reported to play a protective role in cardiac diseases. However, the cellular and molecular mechanisms behind the protective effects of TMP on the heart remain to be elucidated. In this study, we aimed to determine the effects of TMP on angiotensin II (Ang II)-induced hypertrophy in neonatal rat cardiomyocytes and its possible mechanisms of action. In addition, we investigated whether TMP regulates tumor necrosis factor-α (TNF-α) secretion and expression. We found that TMP significantly inhibited the Ang II-induced hypertrophic growth of neonatal cardiomyocytes, as evidenced by the decrease in [3H]leucine incorporation and β-myosin heavy chain (β-MHC) mRNA expression. TMP inhibited Ang II-stimulated TNF-α protein secretion and mRNA expression in the cardiomyocytes. Further experiments revealed that Ang II increased the level of the phosphorylated form of the transcription factor, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), as well as NF-κB-DNA binding activity in the cardiomyocytes; treatment with TMP significantly inhibited the Ang II-induced activation of NF-κB. Furthermore, the inhibition of NF-κB by the specific inhibitor, pyrrolidine dithiocarbamate (PDTC), markedly attenuated the Ang II-induced increase in [3H]leucine incorporation, β-MHC mRNA expression and TNF-α protein secretion. Our findings suggest that TMP inhibits Ang II-induced cardiomyocyte hypertrophy and TNF-α production through the suppression of the NF-κB pathway, which may provide new insight into the mechanisms underlying the protective effects of TMP in heart diseases.
authors.affiliation: School of Basic Medicine, Hubei University of Science and Technology, Xianning, Hubei 437100, P.R. China.
authors.forename: Liangzhu
authors.initials: L
authors.lastname: Yu
authors.forename: Tonghui
authors.initials: T
authors.lastname: She
authors.forename: Mincai
authors.initials: M
authors.lastname: Li
authors.forename: Chunrong
authors.initials: C
authors.lastname: Shi
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.forename: Menglin
authors.initials: M
authors.lastname: Cheng
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006984:Hypertrophy; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D016328:NF-kappa B; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; C017953:tetramethylpyrazine