scholarly journals AMPK as a Potential Therapeutic Target for Intervertebral Disc Degeneration

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhen Wang ◽  
Jianxiong Shen ◽  
Erwei Feng ◽  
Yang Jiao
Keyword(s):  
Protein Kinase ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Therapeutic Target ◽  
Intervertebral Disc Degeneration ◽  
Cell Metabolism ◽  
Activation Process ◽  
Cellular Processes ◽  
Disc Cells ◽  
Remodeling Of Extracellular Matrix

As the principal reason for low back pain, intervertebral disc degeneration (IDD) affects the health of people around the world regardless of race or region. Degenerative discs display a series of characteristic pathological changes, including cell apoptosis, senescence, remodeling of extracellular matrix, oxidative stress and inflammatory local microenvironment. As a serine/threonine-protein kinase in eukaryocytes, AMP-activated protein kinase (AMPK) is involved in various cellular processes through the modulation of cell metabolism and energy balance. Recent studies have shown the abnormal activity of AMPK in degenerative disc cells. Besides, AMPK regulates multiple crucial biological behaviors in IDD. In this review, we summarize the pathophysiologic changes of IDD and activation process of AMPK. We also attempt to generalize the role of AMPK in the pathogenesis of IDD. Moreover, therapies targeting AMPK in alleviating IDD are analyzed, for better insight into the potential of AMPK as a therapeutic target.

scholarly journals Calcitonin inhibits intervertebral disc degeneration by regulating protein kinase C

2020 ◽  
Vol 24 (15) ◽  
pp. 8650-8661
Author(s):  
Jun Ge ◽  
Xiaoqiang Cheng ◽  
Qi Yan ◽  
Cenhao Wu ◽  
Yingjie Wang ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Kinase C

scholarly journals Overexpression of BNIP3 in Rat Intervertebral Disc Cells Can Trigger Autophagy-Related Apoptosis

2020 ◽  
Author(s):  
Ting-Sheng Wu ◽  
Shao-Yong Fan ◽  
Bin Zhang ◽  
Zhi-Qiang Tao ◽  
Hong Hua ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Low Back ◽  
Rt Pcr ◽  
Cell Staining ◽  
Apoptotic Protein ◽  
Disc Cells ◽  
Related Proteins ◽  
Western Blotting Assay

Abstract Background: Intervertebral disc degeneration (IDD) is the important cause of low back pain. Excessive apoptosis of intervertebral disc cells is the primary cause of IDD. BNIP3 is a member of Bcl-2 family and is widely involved in cell autophagy and apoptosis. However, the roles and mechanisms of BNIP3 in intervertebral disc cell autophagy and apoptosis are unclear.Results: In this study, the primary rat intervertebral disc cells were prepared and applied to study the effect of BNIP3 overexpression on their autophagy and apoptosis. RT-PCR and western blotting assay showed that BNIP3 overexpression significantly up-regulated the expression of autophagy and pro-apoptotic related proteins, including HIF-1α, Apaf-1, cleaved caspase 3, LC-3 and Beclin-1, while down-regulated the expression of anti-apoptotic protein Bcl-2. Subsequent cell staining detection of autophagy and apoptosis showed that BNIP3 overexpression significantly increased the autophagy and apoptosis of rat intervertebral disc cells. Furthermore, BNIP3 interference assay revealed that the effects of BNIP3 overexpression can be reversed by BNIP3 interference. Conclusions: The above findings suggested that BNIP3 enhanced autophagy of intervertebral disc cells and further triggered the apoptosis of intervertebral disc cells, eventually led to the development of intervertebral disc degeneration.

scholarly journals Acidic pH promotes intervertebral disc degeneration: Acid-sensing ion channel -3 as a potential therapeutic target

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Hamish T. J. Gilbert ◽  
Nathan Hodson ◽  
Pauline Baird ◽  
Stephen M. Richardson ◽  
Judith A. Hoyland
Keyword(s):  
Intervertebral Disc ◽  
Ion Channel ◽  
Disc Degeneration ◽  
Therapeutic Target ◽  
Intervertebral Disc Degeneration ◽  
Acidic Ph ◽  
Potential Therapeutic Target

scholarly journals The Natural Polyphenol Epigallocatechin Gallate Protects Intervertebral Disc Cells from Oxidative Stress

2016 ◽  
Vol 2016 ◽  
pp. 1-17 ◽  
Author(s):  
Olga Krupkova ◽  
Junichi Handa ◽  
Marian Hlavna ◽  
Juergen Klasen ◽  
Caroline Ospelt ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Epigallocatechin Gallate ◽  
Proliferative Capacity ◽  
Suitable Candidate ◽  
Viable Cells ◽  
Natural Polyphenol ◽  
Disc Cells

Oxidative stress-related phenotypic changes and a decline in the number of viable cells are crucial contributors to intervertebral disc degeneration. The polyphenol epigallocatechin 3-gallate (EGCG) can interfere with painful disc degeneration by reducing inflammation, catabolism, and pain. In this study, we hypothesized that EGCG furthermore protects against senescence and/or cell death, induced by oxidative stress. Sublethal and lethal oxidative stress were induced in primary human intervertebral disc cells with H2O2(totaln=36). Under sublethal conditions, the effects of EGCG on p53-p21 activation, proliferative capacity, and accumulation of senescence-associatedβ-galactosidase were tested. Further, the effects of EGCG on mitochondria depolarization and cell viability were analyzed in lethal oxidative stress. The inhibitor LY249002 was applied to investigate the PI3K/Akt pathway. EGCG inhibited accumulation of senescence-associatedβ-galactosidase but did not affect the loss of proliferative capacity, suggesting that EGCG did not fully neutralize exogenous radicals. Furthermore, EGCG increased the survival of IVD cells in lethal oxidative stress via activation of prosurvival PI3K/Akt and protection of mitochondria. We demonstrated that EGCG not only inhibits inflammation but also can enhance the survival of disc cells in oxidative stress, which makes it a suitable candidate for the development of novel therapies targeting disc degeneration.

scholarly journals LDHA-Mediated Glycolytic Metabolism in Nucleus Pulposus Cells Is a Potential Therapeutic Target for Intervertebral Disc Degeneration

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Longxi Wu ◽  
Jieliang Shen ◽  
Xiaojun Zhang ◽  
Zhenming Hu
Keyword(s):  
Energy Metabolism ◽  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Therapeutic Target ◽  
Intervertebral Disc Degeneration ◽  
Control Group ◽  
Potential Therapeutic Target ◽  
Strong Activity ◽  
Upstream Gene

The intervertebral disc degeneration (IDD) is considered to be an initiator of a series of spinal diseases, among which changes in the nucleus pulposus (NP) are the most significant. NP cells reside in a microenvironment with a lack of blood vessels, hypoxia, and low glucose within the intervertebral disc. Due to the strong activity of HIF-1α, glycolysis is the main pathway for energy metabolism in NP cells. Our previous study found that higher SIRT1 expression is beneficial to delay the degeneration of NP cells. In order to find the downstream genes by which SIRT1 acts on NP cells, we used iTRAQ sequencing to detect the differences between degenerated NP cells overexpressing SIRT1 and a control group (human NP cells were derived from surgery) and found that the expression of LDHA changed in the same direction with SIRT1. This suggests that SIRT1 may delay the degeneration of NP cells by regulating glycolysis. We then used a Seahorse XFe24 analyzer to measure the bioenergetic parameters of NP cells and obtained three findings: (a) glycolysis is the main energy metabolism pathway in NP cells, (b) there is a large difference in ATP production between senescent cells and young cells, and (c) SIRT1 can regulate the production of ATP from glycolysis by regulating LDHA. We also found that SIRT1 in NP cells has a positive regulatory effect on c-Myc which is an upstream gene of LDHA. Through observing IDD-related indicators such as apoptosis, proliferation, senescence, and extracellular matrix, we found that SIRT1 can delay degeneration, and interference with c-Myc and LDHA, respectively, weakens the protective effect of SIRT1. Interfering with LDHA alone can also inhibit glycolysis and accelerate degeneration. Overall, we found that the inhibition of glycolysis in Np cells significantly affects their normal physiological functions and determined that LDHA is a potential therapeutic target for the treatment of IDD.

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