3,3'-Diindolylmethane attenuates cardiac H9c2 cell hypertrophy through 5'-adenosine monophosphate-activated protein kinase-α.

Abstract

3,3'-Diindolylmethane (DIM) is the major product of the acid-catalyzed condensation of indole-3-carbinol (I3C), a component of extracts of Brassica food plants. Numerous studies have suggested that DIM has several beneficial biological activities, including elimination of free radicals, antioxidant and anti-angiogenic effects and activation of apoptosis of various tumor cells. In the present study, an in vitro model was established, using 1 µM angiotensin II (Ang II) in cultured rat cardiac H9c2 cells, to observe the effects of DIM on cardiac hypertrophy. Following 24 h stimulation with DIM (1, 5, and 10 µM) with or without Ang II, cells were characterized by immunofluorescence to analyze cardiac α-actinin expression. Cardiomyocyte hypertrophy and molecular markers of cardiac hypertrophy were assessed by quantitative polymerase chain reaction. Atrial natriuretic peptide, brain natriuretic peptide and myosin heavy chain β mRNA expression were induced by Ang II in H9c2 cells treated with the optimal concentration of DIM for 6, 12, and 24 h. The levels of phosphorylated and total proteins of the 5' AMP-activated protein kinase α (AMPKα)/mitogen-activated protein kinase (MAPK)/mechanistic target of rapamycin (mTOR) signaling pathways in H9c2 cells treated with DIM for 0, 15, 30, and 60 min induced by Ang II were determined by western blot analysis. The results showed that DIM attenuated cellular hypertrophy in vitro, enhanced the phosphorylation of AMPKα and inhibited the MAPK‑mTOR signaling pathway in response to hypertrophic stimuli.

• Authors: Jing Zong, Qing-Qing Wu, Heng Zhou, Jie-Yu Zhang, Yuan Yuan, Zhou-Yan Bian, Wei Deng, Jia Dai, Fang-Fang Li, Man Xu, Yi Fang, Qi-Zhu Tang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 1 Pg. 1247-52 (Jul 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25816057 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cardiotonic Agents
• Indoles
• MYH7 protein, rat
• Vasoconstrictor Agents
• Angiotensin II
• Natriuretic Peptide, Brain
• Atrial Natriuretic Factor
• mTOR protein, rat
• TOR Serine-Threonine Kinases
• AMP-Activated Protein Kinases
• Myosin Heavy Chains
• 3,3'-diindolylmethane

Topics

• AMP-Activated Protein Kinases (antagonists & inhibitors, genetics, metabolism)
• Angiotensin II (pharmacology)
• Animals
• Atrial Natriuretic Factor (genetics, metabolism)
• Cardiomegaly (genetics, metabolism, pathology, prevention & control)
• Cardiotonic Agents (pharmacology)
• Cell Line
• Gene Expression Regulation
• Indoles (pharmacology)
• Models, Biological
• Myocytes, Cardiac (drug effects, metabolism, pathology)
• Myosin Heavy Chains (genetics, metabolism)
• Natriuretic Peptide, Brain (genetics, metabolism)
• Phosphorylation (drug effects)
• Rats
• Signal Transduction
• TOR Serine-Threonine Kinases (antagonists & inhibitors, genetics, metabolism)
• Vasoconstrictor Agents (antagonists & inhibitors, pharmacology)