Neferine modulates IGF-1R/Nrf2 signaling in doxorubicin treated H9c2 cardiomyoblasts.

Abstract

Doxorubicin (DOX) induced cardiotoxicity is a major problem during chemotherapy of cancers. DOX-mediated suppression of type 1 IGF receptor (IGF-1R) signaling leads to cardiac dysfunction. Neferine, a bisbezylisoquinoline alkaloid from the seed embryos of Nelumbo nucifera Gaertn possesses a distinct range of pharmacological properties. Herewith, the present study attempts to elucidate the protective role of neferine against DOX induced toxicity in H9c2 rat cardiomyoblast cell line model. DOX-treated H9c2 cells significantly increased mitochondrial superoxide generation, depleted cellular antioxidant status, suppressed the activation of IGF-1R signaling via PI3K/Akt/mTOR and induced autophagy by the activation of ULK1, Beclin1, Atg7, and LC3B. Neferine pre-treatment activated IGF-1R signaling, improved cellular antioxidant pool, increased the expression of down-stream targets of IGF-1R, such as PI3K/Akt/mTOR, inhibited mitochondrial superoxide generation and autophagy significantly with the induction of Nrf2 translocation and expressions of HO1 and SOD1. Our study suggests the use of neferine for amelioration of DOX-mediated cardiotoxicity.

• Authors: Lohanathan Bharathi Priya, Rathinasamy Baskaran, Chih-Yang Huang, Viswanadha Vijaya Padma
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 119 Issue 2 Pg. 1441-1452 (02 2018) ISSN: 1097-4644 [Electronic] United States
• PMID: 28731223 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Benzylisoquinolines
• NF-E2-Related Factor 2
• Nfe2l2 protein, rat
• Plant Extracts
• neferine
• Doxorubicin
• Heme Oxygenase-1
• Sod1 protein, rat
• Superoxide Dismutase-1
• Receptor, IGF Type 1

Topics

• Animals
• Autophagy (drug effects)
• Benzylisoquinolines (pharmacology)
• Cell Line
• Doxorubicin (adverse effects)
• Gene Expression Regulation (drug effects)
• Heme Oxygenase-1 (metabolism)
• Lipid Peroxidation (drug effects)
• Myocytes, Cardiac (cytology, drug effects, metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Nelumbo (chemistry)
• Plant Extracts (chemistry)
• Rats
• Receptor, IGF Type 1 (metabolism)
• Signal Transduction (drug effects)
• Superoxide Dismutase-1 (metabolism)