Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROS/P38 MAPK-Regulated Inflammatory Responses and Apoptosis
| العنوان: | Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROS/P38 MAPK-Regulated Inflammatory Responses and Apoptosis |
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| المؤلفون: | Gang Chen, Yu-Zhen Han, Zhiqiang Zhang, Jinying Zhang, Shuqing Cui, Qing Nian |
| المصدر: | Oxidative Medicine and Cellular Longevity, Vol 2020 (2020) Oxidative Medicine and Cellular Longevity |
| بيانات النشر: | Hindawi Limited, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, Paraquat, Aging, Article Subject, p38 mitogen-activated protein kinases, Acute Lung Injury, Interleukin-1beta, Apoptosis, Pharmacology, Lung injury, p38 Mitogen-Activated Protein Kinases, Biochemistry, Lipid peroxidation, Mice, chemistry.chemical_compound, Animals, Humans, Viability assay, Klotho Proteins, Klotho, Glucuronidase, Membrane Potential, Mitochondrial, chemistry.chemical_classification, A549 cell, Reactive oxygen species, QH573-671, Interleukin-6, Cell Biology, General Medicine, Mice, Inbred C57BL, Disease Models, Animal, chemistry, A549 Cells, Lipid Peroxidation, Cytology, Signal Transduction, Research Article |
| الوصف: | Acute lung injury (ALI) induced by paraquat (PQ) progresses rapidly with high mortality; however, there is no effective treatment, and the specific mechanism is not well understood. The antiaging protein klotho (KL) has multiple functions and exerts significant influences on various pathophysiological processes. This work evaluated the impact of KL on PQ-induced ALI and investigated its underlying mechanisms. As for in vivo research, C57BL/6 mice were treated with PQ (30 mg/kg) intraperitoneal (IP) injection to create a toxicity model of ALI (PQ group). The mice were divided into control group, KL group, PQ group, and PQ+KL group. For in vitro experiment, A549 cells were incubated with or without KL and then treated in the presence or absence of PQ for 24 h. In vivo result indicated that KL reduced the mortality, reduced IL-1β and IL-6 in the bronchoalveolar lavage fluid (BALF), attenuated ALI, and decreased apoptosis in situ. In vitro result revealed that KL significantly improved cell viability, reduced the levels of IL-1β and IL-6 in culture supernatants, suppressed cell apoptosis, inhibited caspase-3 activation, and enhanced mitochondrial membrane potential (ΔΨm) after PQ treatment. Besides, KL effectively abated reactive oxygen species (ROS) production, improved GSH content, and lowered lipid peroxidation in PQ-exposed A549 cells. Further experiments indicated that phosphorylated JNK and P38 MAPK was increased after PQ treatment; however, KL pretreatment could significantly lower the phosphorylation of P38 MAPK. Suppression of P38 MAPK improved cell viability, alleviated inflammatory response, and reduced apoptosis-related signals; however, it had no obvious effect on the production of ROS. Treatment with N-acetylcysteine (NAC), a classic ROS scavenger, could suppress ROS production and P38 MAPK activation. These findings suggested that KL could alleviate PQ-caused ALI via inhibiting ROS/P38 MAPK signaling-regulated inflammatory responses and mitochondria-dependent apoptosis. |
| وصف الملف: | text/xhtml |
| اللغة: | English |
| تدمد: | 1942-0994 1942-0900 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24e39b4614ee5ec370b0110ae821b532 https://doaj.org/article/386f63ffe67e4e559844ad2833a1b809 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....24e39b4614ee5ec370b0110ae821b532 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19420994 19420900 |
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