Parkin-mediated mitophagy protects against TNF-?-induced stress in bone marrow mesenchymal stem cells

被引：9
作者：
Fan, Pan [1 ]
Yu, Xiao-Yu [2 ]
Chen, Chang-Hong [3 ]
Gao, Jia-Wei [1 ]
Xu, Yu-Zhu [1 ]
Xie, Xin-Hui [1 ,4 ]
Wang, Yun-Tao [1 ,4 ]
机构：
[1] Southeast Univ, Zhongda Hosp, Dept Spine Ctr, Med Sch, Nanjing, Peoples R China
[2] Nanjing Med Univ, Affiliated Jiangning Hosp, Dept gynaecol & Obstet, Nanjing, Peoples R China
[3] Nanjing Univ Chinese Med, Jiangyin Affiliated Hosp, Dept Orthopaed Surg, Nanjing, Peoples R China
[4] Southeast Univ, Zhongda Hosp, Sch Med, 87 Dingjiaqiao, Nanjing 210009, Jiangsu, Peoples R China
来源：
EXPERIMENTAL GERONTOLOGY | 2022年 / 164卷
基金：
中国国家自然科学基金;
关键词：
Mitophagy; Bone marrow mesenchymal stem cell; Oxidative stress; TNF-; Senescence; NUCLEUS PULPOSUS CELLS; MITOCHONDRIA; SENESCENCE; ALPHA; PROLIFERATION; DEGRADATION; DISC;
D O I：
10.1016/j.exger.2022.111829
中图分类号：
R592 [老年病学]; C [社会科学总论];
学科分类号：
03 ; 0303 ; 100203 ;
摘要：
Bone marrow mesenchymal stem cells (BMSCs) have been investigated as cellular therapeutics for intervertebral disc degeneration. However, transplanted BMSCs are prone to be damaged. TNF-alpha is reported to extensively promote degeneration process. Nevertheless, the relationship between BMSCs senescence and TNF-alpha-induced stress has not been elucidated. Previous studies showed that mitophagy is a crucial factor in maintaining cellular homeostasis. Hence, we sought to clarify the role and mechanism of mitophagy in TNF-alpha-induced biological changes of BMSCs. Here, we found that TNF-alpha caused transient senescent damage in the early stage. Meanwhile, Parkin-mediated mitophagy was initiated and weakened the damage through maintaining mitochondria homeostasis. After inhibiting mitophagy by knockdown of Parkin, TNF-alpha irreversibly caused cellular senescence. These results suggested that Parkin-mediated mitophagy played protective role in BMSCs in response to TNF-alpha, which could be a crucial therapeutic target in the future.
引用
收藏
页数：11
相关论文
共 38 条
[1]   MONITORING AUTOPHAGIC DEGRADATION OF P62/SQSTM1 [J].
Bjorkoy, Geir ;
Lamark, Trond ;
Pankiv, Serhiy ;
Overvatn, Aud ;
Brech, Andreas ;
Johansen, Terje .
METHODS IN ENZYMOLOGY: AUTOPHAGY IN MAMMALIAN SYSTEMS, VOL 452, PT B, 2009, 452 :181-197
[2]   Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue [J].
Boengler, Kerstin ;
Kosiol, Maik ;
Mayr, Manuel ;
Schulz, Rainer ;
Rohrbach, Susanne .
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, 2017, 8 (03) :349-369
[3]   Interaction between ROS dependent DNA damage, mitochondria and p38 MAPK underlies senescence of human adult stem cells [J].
Borodkina, Aleksandra ;
Shatrova, Alla ;
Abushik, Polina ;
Nikolsky, Nikolay ;
Burova, Elena .
AGING-US, 2014, 6 (06) :481-495
[4]   Oxidative stress induces senescence in human mesenchymal stem cells [J].
Brandl, Anita ;
Meyer, Matthias ;
Bechmann, Volker ;
Nerlich, Michael ;
Angele, Peter .
EXPERIMENTAL CELL RESEARCH, 2011, 317 (11) :1541-1547
[5]   The role of mitochondria in aging [J].
Bratic, Ana ;
Larsson, Nils-Goran .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (03) :951-957
[6]   Sublethal Oxidative Stress Induces the Premature Senescence of Human Mesenchymal Stem Cells Derived from Endometrium [J].
Burova, Elena ;
Borodkina, Aleksandra ;
Shatrova, Alla ;
Nikolsky, Nikolay .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2013, 2013
[7]   Mitochondrial mass governs the extent of human T cell senescence [J].
Callender, Lauren A. ;
Carroll, Elizabeth C. ;
Bober, Emilia A. ;
Akbar, Arne N. ;
Solito, Egle ;
Henson, Sian M. .
AGING CELL, 2020, 19 (02)
[8]   Endoplasmic Reticulum Stress Facilitates the Survival and Proliferation of Nucleus Pulposus Cells in TNF-α Stimulus by Activating Unfolded Protein Response [J].
Chen, Lu ;
Liu, Lei ;
Xie, Zhi-Yang ;
Wang, Feng ;
Sinkemani, Arjun ;
Zhang, Cong ;
Wang, Xiao-Hu ;
Wang, Kun ;
Hong, Xin ;
Wu, Xiao-Tao .
DNA AND CELL BIOLOGY, 2018, 37 (04) :347-358
[9]   Protein kinase RNA-like ER kinase/eukaryotic translation initiation factor 2 pathway attenuates <bold>tumor necrosis factor alpha-induced apoptosis in nucleus pulposus cells by activating autophagy</bold> [J].
Chen, Lu ;
Liu, Lei ;
Xie, Zhi-Yang ;
Wang, Feng ;
Zhu, Lei ;
Zhang, Cong ;
Fan, Pan ;
Sinkemani, Arjun ;
Hong, Xin ;
Wu, Xiao-Tao .
JOURNAL OF CELLULAR PHYSIOLOGY, 2019, 234 (07) :11631-11645
[10]   Nuclear factor-kappa B-dependent X-box binding protein 1 signalling promotes the proliferation of nucleus pulposus cells under tumour necrosis factor alpha stimulation [J].
Chen, Lu ;
Xie, Zhi-Yang ;
Liu, Lei ;
Zhu, Lei ;
Wang, Feng ;
Fan, Pan ;
Sinkemani, Arjun ;
Zhang, Cong ;
Hong, Xin ;
Wu, Xiao-Tao .
CELL PROLIFERATION, 2019, 52 (02)
1234