Xiuping Lin,Chang-sheng Shao,Shereen M. Elsherbiny,Qing Huang
Astaxanthin (AST) is a xanthophyll carotenoid with strong oxidation resistance, which can effectively scavenge various free radicals and protect organisms from oxidative damage. AST is also known to have prominent anti-aging effects, but the underlying mechanism of AST in anti-radiation aging is largely unknown. In this work, we applied ultraviolet (UV) irradiation to accelerate the aging of Caenorhabditis elegans ( C. elegans ) and treated the nematodes with AST to explore whether and how AST could attenuate the radiation-induced aging effect. Our results showed that AST improved the survival rate of C. elegans , reduced the aging biomarkers, and alleviated the mitochondrial dysfunction caused by the irradiation. Based on the transcriptome sequencing analysis, we identified that the key genes regulated by AST were involved in JNK-MAPK and DAF-16 longevity signaling pathways. Furthermore, we employed jnk-1 and daf-16 mutants and verified the role of the JNK-1/DAF-16 signaling pathway in the anti-aging effect. As such, this study has not only demonstrated that AST can resist the aging process caused by UV-irradiation but also revealed the anti-aging mechanism of AST through JNK-1/DAF-16 activation in C. elegans.
Yan Luo,Daogong Zhang,Yueling Chen,Zhongsheng Cao,Zhaomin Fan
The brain‑derived neurotrophic factor (BDNF) and c‑Jun NH 2‑terminal kinase (JNK) signaling pathways are therapeutic targets to prevent degeneration in the central nervous system. Dexamethasone (DXMS), a glucocorticoid, protects against vestibular brain injury, however, the molecular mechanisms have yet to be fully elucidated. To investigate whether the BDNF and JNK signaling pathways are involved in the protective effects of DXMS in rats with vestibular dysfunction, a rat model of severe vestibular deficits was established by middle ear injection of arsanilic acid (AA; 100 mg/ml; 0.05 ml). After 3 days, rat symptoms and behavior scores with vestibular disorders were detected. In brain tissues, histopathological alterations, cell apoptosis, expression levels and patterns of BDNF signaling pathway‑associated BDNF, tyrosine receptor kinase B (TrKB) and K+/Cl‑ cotransporter isoform 2 (KCC2), and the expression of apoptosis‑related cleaved‑caspase 3 and the JNK signaling pathway were detected. It was identified that DXMS relieved AA‑induced vestibular dysfunction, leading to improvement in rat behavior scores to normal levels, minimizing brain damage at the histopatholojnnkngical level, reducing cell apoptosis, enhancing the expression of BDNF, TrKB and KCC2, and downregulating cleaved‑caspase 3 and phosphorylated‑JNK1/2 in brain tissues. Together, these findings indicated the protective effect of DXMS on AA‑induced rat vestibular dysfunction, and that activating BDNF and inhibiting JNK singling pathways were the underlying mechanisms. In addition, with additional treatment of mifepristone (RU486), a specific glucocorticoid agonist, all the events elicited by DXMS mentioned above in the AA‑treated rat rats were reversed. In conclusion, DXMS was identified as a therapeutic agent targeting the BDNF and JNK singling pathways for AA‑induced rat vestibular dysfunction.
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