Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROSP38 MAPK-Regulated Inflammatory Responses and Apoptosis
Joint Authors
Zhang, Zhiqiang
Nian, Qing
Chen, Gang
Cui, Shuqing
Han, Yuzhen
Zhang, Jinying
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-13, 13 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-05-14
Country of Publication
Egypt
No. of Pages
13
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Zhang, Zhiqiang& Nian, Qing& Chen, Gang& Cui, Shuqing& Han, Yuzhen& Zhang, Jinying. 2020. Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROSP38 MAPK-Regulated Inflammatory Responses and Apoptosis. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1203840
Modern Language Association (MLA)
Zhang, Zhiqiang…[et al.]. Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROSP38 MAPK-Regulated Inflammatory Responses and Apoptosis. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-13.
https://search.emarefa.net/detail/BIM-1203840
American Medical Association (AMA)
Zhang, Zhiqiang& Nian, Qing& Chen, Gang& Cui, Shuqing& Han, Yuzhen& Zhang, Jinying. Klotho Alleviates Lung Injury Caused by Paraquat via Suppressing ROSP38 MAPK-Regulated Inflammatory Responses and Apoptosis. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-13.
https://search.emarefa.net/detail/BIM-1203840
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1203840