Therapeutic effect of psoralen on muscle atrophy induced by tumor necrosis factor-α

• Main Authors: Xin-Feng Lin, Qi-Long Jiang, Zhi-Long Peng, Yi-Le Ning, Yuan-Yuan Luo, Fu Zhao, Xian Peng, Wei-Tao Chen
• Format: Article
• Language: English
• Published: Mashhad University of Medical Sciences 2020-02-01
• Series: Iranian Journal of Basic Medical Sciences
• Subjects: c2c12; mir-675-5p; muscle atrophy; psoralen; tumor necrosis factor α
• Online Access: http://ijbms.mums.ac.ir/article_14290_23547c70f0455d2e3f0811bf0e8c7228.pdf
• ISSN: 2008-3866; 2008-3874

<em><strong>Objective(s):</strong></em> To observe and determine the effect and mechanism of psoralen on tumor necrosis factor-α (TNF-α)-induced muscle atrophy.<br /><em><strong>Materials and Methods:</strong></em> Three sets of C2C12 cells, including blank control, TNF-α (10 or 20 ng/ml) treatment and a TNF-α (10 or 20 ng/ml) plus psoralen (80 μM) administration were investigated. Cell viability was assessed using Cell Counting Kit-8 (CCK-8) assay. Western blot analysis was used to detect protein expression of atrophic markers. Flowcytometry was used to observe the effect of psoralen on apoptosis. A quantitative real-time PCR (qRT-PCR) assay was performed to detect the mRNA level of miR-675-5P.<br /><em><strong>Results:</strong></em> TNF-α (1, 10, 20 and 100 ng/ml) treatment inhibited C2C12 myoblast viability (P<0.001), while 24 hr of psoralen administration increased the viability, and lowered TNF-α cytotoxicity (P<0.001). MURF1, MAFbx, TRIM62 and GDF15 expressions were significantly increased in TNF-α (10 ng/ml or 20 ng/ml)-treated group (P<0.001), and psoralen could significantly decrease the expression of these proteins (P<0.001). Apoptotic rate of C2C12 myoblasts was increased after TNF-α (10 ng/ml and 20 ng/ml) treatment, and was significantly decreased after psoralen treatment (P<0.001). miR-675-5P was increased in TNF-α-treated C2C12 myoblasts compared to control group, and it was significantly decreased after psoralen treatment.<br /><em><strong>Conclusion:</strong></em> Psoralen could reduce TNF-α-induced cytotoxicity, atrophy and apoptosis in C2C12 myoblasts. The therapeutic effect of psoralen may be achieved by down-regulating miR-675-5P.