Compression‐induced senescence of nucleus pulposus cells by promoting mitophagy activation via the PINK1/PARKIN pathway

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The current research aimed to explore the possible relationship between PINK1/PARKIN‐mediated mitophagy and the compression‐induced senescence of nucleus pulposus cells (NPCs). Therefore, the stages of senescence in NPCs were measured under compression lasting 0, 24 and 48 hours. The mitophagy‐related markers, autophagosomes and mitochondrial membrane potential were tested to determine the levels of PINK1/PARKIN‐mediated mitophagy under compression. The PINK1 and PARKIN levels were also measured by immunohistochemistry of human and rat intervertebral disc (IVD) tissues taken at different degenerative stages. A specific mitophagy inhibitor, cyclosporine A (CSA) and a constructed PINK1‐shRNA were used to explore the relationship between mitophagy and senescence by down‐regulating the PINK1/PARKIN‐mediated mitophagy levels. Our results indicated that compression significantly enhanced the senescence of NPCs in a time‐dependent manner. Also, PINK1/PARKIN‐mediated mitophagy was found to be activated by the extended duration of compression on NPCs as well as the increased degenerative stages of IVD tissues. After inhibition of PINK1/PARKIN‐mediated mitophagy by CSA and PINK1‐shRNA, the senescence of NPCs induced by compression was strongly rescued. Hence, the excessive degradation of mitochondria in NPCs by mitophagy under continuous compression may accelerate the senescence of NPCs. Regulating PINK1/PARKIN‐mediated mitophagy might be a potential therapeutic treatment for IVD degeneration.

Related collections

Most cited references 43

Record: found
Abstract: found
Article: not found

Forging a signature of in vivo senescence.

Norman E. Sharpless, Charles J Sherr (2015)

'Cellular senescence', a term originally defining the characteristics of cultured cells that exceed their replicative limit, has been broadened to describe durable states of proliferative arrest induced by disparate stress factors. Proposed relationships between cellular senescence, tumour suppression, loss of tissue regenerative capacity and ageing suffer from lack of uniform definition and consistently applied criteria. Here, we highlight caveats in interpreting the importance of suboptimal senescence-associated biomarkers, expressed either alone or in combination. We advocate that more-specific descriptors be substituted for the now broadly applied umbrella term 'senescence' in defining the suite of diverse physiological responses to cellular stress.

0 comments Cited 429 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1

Jun-Li Xiao, Xiaoxuan Xu, Fan Zhang … (2016)

Mitochondria play a crucial role in tubular injury in diabetic kidney disease (DKD). MitoQ is a mitochondria-targeted antioxidant that exerts protective effects in diabetic mice, but the mechanism underlying these effects is not clear. We demonstrated that mitochondrial abnormalities, such as defective mitophagy, mitochondrial reactive oxygen species (ROS) overexpression and mitochondrial fragmentation, occurred in the tubular cells of db/db mice, accompanied by reduced PINK and Parkin expression and increased apoptosis. These changes were partially reversed following an intraperitoneal injection of mitoQ. High glucose (HG) also induces deficient mitophagy, mitochondrial dysfunction and apoptosis in HK-2 cells, changes that were reversed by mitoQ. Moreover, mitoQ restored the expression, activity and translocation of HG-induced NF-E2-related factor 2 (Nrf2) and inhibited the expression of Kelch-like ECH-associated protein (Keap1), as well as the interaction between Nrf2 and Keap1. The reduced PINK and Parkin expression noted in HK-2 cells subjected to HG exposure was partially restored by mitoQ. This effect was abolished by Nrf2 siRNA and augmented by Keap1 siRNA. Transfection with Nrf2 siRNA or PINK siRNA in HK-2 cells exposed to HG conditions partially blocked the effects of mitoQ on mitophagy and tubular damage. These results suggest that mitoQ exerts beneficial effects on tubular injury in DKD via mitophagy and that mitochondrial quality control is mediated by Nrf2/PINK.

0 comments Cited 209 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration.

F. Wang, F Cai, R Shi … (2016)

Intervertebral disc (IVD) degeneration is a complicated process that involves both age-related change and tissue damage caused by multiple stresses. In a degenerative IVD, cellular senescence accumulates and is associated with reduced proliferation, compromised self-repair, increased inflammatory response, and enhanced catabolic metabolism. In this review, we decipher the senescence mechanism of IVD degeneration (IVDD) by interpreting how aging coordinates with age-related, microenvironment-derived stresses in promoting disc cell senescence and accelerating IVDD. After chronic and prolonged replication, cell senescence may occur as a natural part of the disc aging process, but can potentially be accelerated by growth factor deficiency, oxidative accumulation, and inflammatory irritation. While acute disc injury, excessive mechanical overloading, diabetes, and chronic tobacco smoking contribute to the amplification of senescence-inducing stresses, the avascular nature of IVD impairs the immune-clearance of the senescent disc cells, which accumulate in cell clusters, demonstrate inflammatory and catabolic phenotypes, deteriorate disc microenvironment, and accelerate IVDD. Anti-senescence strategies, including telomerase transduction, supply of growth factors, and blocking cell cycle inhibitors, have been shown to be feasible in rescuing disc cells from early senescence, but their efficiency for disc regeneration requires more in vivo validations. Guidelines dedicated to avoiding or alleviating senescence-inducing stresses might decelerate cellular senescence and benefit patients with IVD degenerative diseases.

0 comments Cited 206 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Kaige Ma:

ORCID: https://orcid.org/0000-0003-3099-2170

makaige225@hust.edu.cn

Journal

Journal ID (nlm-ta): J Cell Mol Med

Journal ID (iso-abbrev): J. Cell. Mol. Med

Journal ID (doi): 10.1111/(ISSN)1582-4934

Journal ID (publisher-id): JCMM

Title: Journal of Cellular and Molecular Medicine

Publisher: John Wiley and Sons Inc. (Hoboken )

ISSN (Print): 1582-1838

ISSN (Electronic): 1582-4934

Publication date (Electronic): 12 April 2020

Publication date (Print): May 2020

Volume: 24

Issue: 10 ( doiID: 10.1111/jcmm.v24.10 )

Pages: 5850-5864

Affiliations

[ ¹ ] Department of Orthopaedics Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan China

[ ² ] Department of Orthopedics Musculoskeletal Tumor Center The Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou China

Author notes

[*] [* ] Correspondence

Kaige Ma, Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Email: makaige225@ 123456hust.edu.cn

Author information

Zengwu Shao https://orcid.org/0000-0003-1616-8118

Kaige Ma https://orcid.org/0000-0003-3099-2170

Article

Publisher ID: JCMM15256

DOI: 10.1111/jcmm.15256

PMC ID: 7214186

PubMed ID: 32281308

SO-VID: f58d354c-4cb4-46c0-99a7-c4be238a5595

License:

This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

History

Date received : 03 July 2019

Date revision received : 11 March 2020

Date accepted : 13 March 2020

Page count

Figures: 7, Tables: 0, Pages: 15, Words: 7519

Funding

Funded by: China Postdoctoral Science Foundation , open-funder-registry 10.13039/501100002858;

Award ID: 2019M662077

Funded by: National Natural Science Foundation of China , open-funder-registry 10.13039/501100001809;

Award ID: 81501924

Award ID: 91649204

Funded by: the National Key Research and Development Program of China

Award ID: 2016YFC1100100

Custom metadata

source-schema-version-number 2.0

cover-date May 2020

details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.1 mode:remove_FC converted:11.05.2020

ScienceOpen disciplines: Molecular medicine

Keywords: compression,intervertebral disc,mitophagy,parkin pathway,pink1,senescence

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: compression, intervertebral disc, mitophagy, parkin pathway, pink1, senescence

Compression‐induced senescence of nucleus pulposus cells by promoting mitophagy activation via the PINK1/PARKIN pathway

Read this article at

Abstract

Related collections

Bacterial extracellular vesicles

Most cited references 43

Forging a signature of in vivo senescence.

The mitochondria-targeted antioxidant MitoQ ameliorated tubular injury mediated by mitophagy in diabetic kidney disease via Nrf2/PINK1

Aging and age related stresses: a senescence mechanism of intervertebral disc degeneration.

Author and article information

Contributors

Journal

Affiliations

Author notes

Author information

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 779

Cited by 19

Most referenced authors 563