Muscle p62 stimulates the expression of antioxidant proteins alleviating cancer cachexia

恶病质 骨骼肌 肌肉萎缩 内科学 内分泌学 浪费的 磷酸化 糖酵解 氧化磷酸化 氧化应激 KEAP1型 转录因子 生物 化学 生物化学 癌症 医学 基因 新陈代谢
作者
Mami Yamada,Eiji Warabi,Hisashi Oishi,Vitor A. Lira,Mitsuharu Okutsu
出处
期刊:The FASEB Journal [Wiley]
卷期号:37 (9) 被引量:4
标识
DOI:10.1096/fj.202300349r
摘要

Oxidative stress plays an important role in skeletal muscle atrophy during cancer cachexia, and more glycolytic muscles are preferentially affected. Sequestosome1/SQSTM1 (i.e., p62), particularly when phosphorylated at Ser 349 (Ser 351 in mice), competitively binds to the Kelch-like ECH-associated protein 1 (Keap1) activating Nuclear factor erythroid 2-related factor 2 (Nrf2). Nrf2 then stimulates the transcription of antioxidant/electrophile-responsive elements in target genes. However, a potential role for p62 in the protection of muscle wasting in cachexia remains to be determined. Here, using the well-established cachexia-inducing model of Lewis Lung Carcinoma (LLC) in mice we demonstrate higher expression of antioxidant proteins (i.e., NQO1, HO-1, GSTM1, CuZnSOD, MnSOD, and EcSOD) in the more oxidative and cachexia resistant soleus muscle than in the more glycolytic and cachexia prone extensor digitorum longus muscle. This was accompanied by higher p62 (total and phosphorylated) and nuclear Nrf2 levels in the soleus, which were paralleled by higher expression of proteins known to either phosphorylate or promote p62 phosphorylation (i.e., NBR1, CK1, PKCδ, and TAK1). Muscle-specific p62 gain-of-function (i.e., in p62 mTg mice) activated Nrf2 nuclear translocation and increased the expression of multiple antioxidant proteins (i.e., CuZnSOD, MnSOD, EcSOD, NQO1, and GSTM1) in glycolytic muscles. Interestingly, skeletal muscle Nrf2 haplodeficiency blunted the increases of most of these proteins (i.e., CuZnSOD, EcSOD, and NQO1) suggesting that muscle p62 stimulates antioxidant protein expression also via additional, yet to be determined mechanisms. Of note, p62 gain-of-function mitigated glycolytic muscle wasting in LLC-affected mice. Collectively, our findings identify skeletal muscle p62 as a potential therapeutic target for cancer cachexia.
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
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

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
单薄的忆枫完成签到,获得积分10
刚刚
土豆淀粉发布了新的文献求助10
刚刚
1秒前
欣欣完成签到 ,获得积分10
1秒前
2秒前
如意冰棍发布了新的文献求助10
2秒前
嗷嗷发布了新的文献求助10
2秒前
震震应助爱躺平的老baby采纳,获得10
2秒前
2秒前
优雅含莲完成签到 ,获得积分10
3秒前
3秒前
3秒前
Bugatti完成签到,获得积分10
3秒前
量子星尘发布了新的文献求助10
3秒前
4秒前
5秒前
5秒前
自由的白玉完成签到,获得积分20
5秒前
6秒前
hj木秀于林完成签到,获得积分10
6秒前
6秒前
无语的无声完成签到,获得积分10
6秒前
7秒前
稳重的宛丝完成签到 ,获得积分10
7秒前
雪白的灵竹完成签到,获得积分10
7秒前
Owen应助pwy采纳,获得10
8秒前
温柔的婷发布了新的文献求助30
9秒前
FashionBoy应助jiujiu采纳,获得30
10秒前
和谐竺发布了新的文献求助10
10秒前
dfsdf发布了新的文献求助10
10秒前
10秒前
背后如雪发布了新的文献求助10
10秒前
11秒前
12秒前
12秒前
12秒前
13秒前
pluto应助小玲玲采纳,获得10
13秒前
14秒前
LL发布了新的文献求助10
15秒前
高分求助中
(应助此贴封号)【重要!!请各用户(尤其是新用户)详细阅读】【科研通的精品贴汇总】 10000
计划经济时代的工厂管理与工人状况(1949-1966)——以郑州市国营工厂为例 500
INQUIRY-BASED PEDAGOGY TO SUPPORT STEM LEARNING AND 21ST CENTURY SKILLS: PREPARING NEW TEACHERS TO IMPLEMENT PROJECT AND PROBLEM-BASED LEARNING 500
The Pedagogical Leadership in the Early Years (PLEY) Quality Rating Scale 410
Stackable Smart Footwear Rack Using Infrared Sensor 300
Modern Britain, 1750 to the Present (第2版) 300
Writing to the Rhythm of Labor Cultural Politics of the Chinese Revolution, 1942–1976 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 生物化学 物理 纳米技术 计算机科学 内科学 化学工程 复合材料 物理化学 基因 催化作用 遗传学 冶金 电极 光电子学
热门帖子
关注 科研通微信公众号,转发送积分 4603484
求助须知:如何正确求助?哪些是违规求助? 4012177
关于积分的说明 12422449
捐赠科研通 3692673
什么是DOI,文献DOI怎么找? 2035749
邀请新用户注册赠送积分活动 1068916
科研通“疑难数据库(出版商)”最低求助积分说明 953403