Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride‐induced liver fibrosis

TFAM公司 MFN2型 褪黑素 品脱1 粒体自噬 线粒体生物发生 线粒体分裂 DNM1L型 线粒体 内分泌学 生物 内科学 第一季 线粒体融合 细胞生物学 自噬 细胞凋亡 线粒体DNA 医学 生物化学 基因
作者
Jung‐Woo Kang,Jin Woo Hong,Sun-Mee Lee
出处
期刊:Journal of Pineal Research [Wiley]
卷期号:60 (4): 383-393 被引量:174
标识
DOI:10.1111/jpi.12319
摘要

Abstract Liver fibrosis leads to liver cirrhosis and failure, and no effective treatment is currently available. Growing evidence supports a link between mitochondrial dysfunction and liver fibrogenesis and mitochondrial quality control‐based therapy has emerged as a new therapeutic target. We investigated the protective mechanisms of melatonin against mitochondrial dysfunction‐involved liver fibrosis, focusing on mitophagy and mitochondrial biogenesis. Rats were treated with carbon tetrachloride ( CC l 4 ) dissolved in olive oil (0.5 mL /kg, twice a week, i.p.) for 8 wk. Melatonin was administered orally at 2.5, 5, and 10 mg/kg once a day. Chronic CC l 4 exposure induced collagen deposition, hepatocellular damage, and oxidative stress, and melatonin attenuated these increases. Increases in mRNA and protein expression levels of transforming growth factor β 1 and α ‐smooth muscle actin in response to CC l 4 were attenuated by melatonin. Melatonin attenuated hallmarks of mitochondrial dysfunction, such as mitochondrial swelling and glutamate dehydrogenase release. Chronic CC l 4 exposure impaired mitophagy and mitochondrial biogenesis, and melatonin attenuated this impairment, as indicated by increases in mitochondrial DNA and in protein levels of PTEN ‐induced putative kinase 1 ( PINK 1); Parkin; peroxisome proliferator‐activated receptor‐gamma coactivator 1 α ( PGC ‐1 α ); nuclear respiratory factor 1 ( NRF 1); and transcription factor A, mitochondrial ( TFAM ). CC l 4 ‐mediated decreases in mitochondrial fission‐ and fusion‐related proteins, such as dynamin‐related protein 1 ( DRP 1) and mitofusin 2, were also attenuated by melatonin. Moreover, melatonin induced AMP ‐activated protein kinase ( AMPK ) phosphorylation. These results suggest that melatonin protects against liver fibrosis via upregulation of mitophagy and mitochondrial biogenesis, and may be useful as an anti‐fibrotic treatment.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
2秒前
小蘑菇应助刘小花采纳,获得10
3秒前
6秒前
桐桐应助zhouleiwang采纳,获得10
9秒前
赘婿应助绝尘采纳,获得10
10秒前
刘小花完成签到,获得积分20
11秒前
金晓发布了新的文献求助10
15秒前
17秒前
zmnzmnzmn应助科研通管家采纳,获得10
22秒前
朝暮应助科研通管家采纳,获得10
22秒前
22秒前
Owen应助科研通管家采纳,获得10
22秒前
HEIKU应助科研通管家采纳,获得10
22秒前
今后应助科研通管家采纳,获得10
22秒前
隐形曼青应助科研通管家采纳,获得30
22秒前
orixero应助科研通管家采纳,获得30
22秒前
22秒前
HEIKU应助科研通管家采纳,获得10
22秒前
领导范儿应助科研通管家采纳,获得10
22秒前
22秒前
24秒前
绝尘发布了新的文献求助10
28秒前
28秒前
端庄的连碧完成签到 ,获得积分10
28秒前
行走完成签到,获得积分10
29秒前
30秒前
32秒前
bernoulli发布了新的文献求助10
33秒前
852应助能干数据线采纳,获得10
36秒前
37秒前
华仔应助神经蛙采纳,获得10
38秒前
kk发布了新的文献求助10
38秒前
39秒前
39秒前
纪复天完成签到,获得积分10
39秒前
哭泣嵩发布了新的文献求助10
39秒前
demoliu发布了新的文献求助80
41秒前
zhouleiwang发布了新的文献求助10
43秒前
纪复天发布了新的文献求助10
43秒前
gab发布了新的文献求助10
44秒前
高分求助中
【此为提示信息,请勿应助】请按要求发布求助,避免被关 20000
Continuum Thermodynamics and Material Modelling 2000
Encyclopedia of Geology (2nd Edition) 2000
105th Edition CRC Handbook of Chemistry and Physics 1600
Maneuvering of a Damaged Navy Combatant 650
Периодизация спортивной тренировки. Общая теория и её практическое применение 310
Mixing the elements of mass customisation 300
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3778901
求助须知:如何正确求助?哪些是违规求助? 3324431
关于积分的说明 10218443
捐赠科研通 3039495
什么是DOI,文献DOI怎么找? 1668204
邀请新用户注册赠送积分活动 798591
科研通“疑难数据库(出版商)”最低求助积分说明 758440