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Tanshinone IIA inhibits Leu27IGF-II-induced insulin-like growth factor receptor II signaling and myocardial apoptosis via estrogen receptor-mediated Akt activation.
Chou, Shui Lian; Ramesh, Samiraj; Kuo, Chia-Hua; Ali, Ayaz; Ho, Tsung-Jung; Chang, Ko Peng; Hsieh, Dennis Jine-Yuan; Kumar, V Bharath; Weng, Yueh-Shan; Kuo, Wei-Wen; Huang, Chih-Yang.
Afiliación
  • Chou SL; Department of Family Medicine, Jen-Ai Hospital, Taichung, Taiwan.
  • Ramesh S; Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
  • Kuo CH; Department of Microbiology, PRIST Deemed to be University, Thanjavur, Tamil Nadu, India.
  • Ali A; Department of Sports Sciences, University of Taipei, Taipei, Taiwan.
  • Ho TJ; Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
  • Chang KP; Chinese Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan.
  • Hsieh DJ; Integration Center of Traditional Chinese and Modern Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
  • Kumar VB; Department of Family Medicine, Jen-Ai Hospital, Taichung, Taiwan.
  • Weng YS; School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
  • Kuo WW; Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.
  • Huang CY; Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan.
Environ Toxicol ; 37(1): 142-150, 2022 Jan.
Article en En | MEDLINE | ID: mdl-34655285
Different stress condition stimulates the expression level of insulin-like growth factor receptor II (IGF-IIR) in cardiomyoblasts that lead to apoptosis. Tanshinone IIA (TSN), a pharmacologically active component from Danshen, has been shown cardioprotective effects against cardiac apoptosis induced by several stress conditions. Therefore, this study was conducted to assess the cardioprotective effects of TSN IIA mediated through the estrogen receptor (ER) in order to inhibit the Leu27IGF-II-enhanced IGF-IIR-mediated cardiac apoptosis. The estrogenic activity of TSN IIA was examined after myocardial cells were pretreated with the ER antagonist, and inhibited the phospho-inositide-3 kinase (PI3K). Here, we found that TSN IIA significantly induced ER that phosphorylated Akt. Further, Akt activation considerably suppressed the Leu27IGF-II induced IGF-IIR expression level and the downstream effectors, including Gαq and calcineurin as well as mitochondrial dependent apoptosis proteins including Bad, cytochrome c, and active caspase-3 that result in cardiac apoptosis resistance. However, the western blot analysis, JC-1 staining, and terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay revealed that TSN IIA attenuated Leu27IGF-II-induced IGF-IIR mediated cardiac apoptosis was reversed by an ER antagonist such as ICI 182780, and PI3K inhibition. All these findings demonstrate that TSN IIA exerts estrogenic activity, which can activate PI3K-Akt pathway, and thereby inhibits Leu27IGFII induced IGF-IIR mediated cardiac apoptosis. Thus, TSN IIA can be considered as an effective therapeutic strategy against IGF-IIR signaling cascade to suppress cardiac apoptosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Estrógenos / Receptor IGF Tipo 2 / Miocitos Cardíacos / Abietanos / Proteínas Proto-Oncogénicas c-akt Límite: Animals Idioma: En Revista: Environ Toxicol Asunto de la revista: SAUDE AMBIENTAL / TOXICOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Estrógenos / Receptor IGF Tipo 2 / Miocitos Cardíacos / Abietanos / Proteínas Proto-Oncogénicas c-akt Límite: Animals Idioma: En Revista: Environ Toxicol Asunto de la revista: SAUDE AMBIENTAL / TOXICOLOGIA Año: 2022 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos