Pyrroloquinoline Quinone Protects Nucleus Pulposus Cells from Hydrogen Peroxide-induced Apoptosis by Inhibiting the Mitochondria-mediated Pathway

Overview

Journal Eur Spine J

Specialty Orthopedics

Date 2014 Oct 29

PMID 25349108

Citations 33

Authors

Lianjun Yang

Zijie Rong

Mingjun Zeng

Yanlin Cao

Xumeng Gong

Lijun Lin

Yong Chen

Wei Cao

Lixin Zhu

Weiren Dong

Affiliations

Soon will be listed here.

Abstract

Purpose: Intervertebral disc cell apoptosis has been suggested to play a key role in promoting disc degeneration, and many studies have shown that the mechanism may be related to oxidative stress. Pyrroloquinoline quinone (PQQ), a redox cofactor for bacterial dehydrogenases, possesses the potential to scavenge reactive oxygen species (ROS) and inhibit cell apoptosis. The objective of this study was to evaluate the effects of PQQ on cultured rat nucleus pulposus (NP) cells under conditions of oxidative injury induced by hydrogen peroxide (H2O2) and to investigate the underlying mechanisms in vitro.

Methods: Cell viability was determined by CCK8 assay. Changes in the apoptosis rate, intracellular ROS levels and the mitochondrial membrane potential were measured by flow cytometry. Extracellular matrix (ECM)-related proteins (collagen-2 and aggrecan) and apoptosis-related proteins (Bcl-2, Bax, cytochrome c, and caspase-3) were investigated by western blotting.

Results: The results show that NP cells pretreated with PQQ before H2O2 exposure exhibited increased cell viability, decreased ROS formation, maintained mitochondrial membrane potential, and reduced apoptosis. In the presence of PQQ, ECM production was maintained by the cells despite being in an apoptotic environment. In addition, pretreatment with PQQ increased the expression of Bcl-2, inhibited the release of mitochondrial cytochrome c, and decreased the expressions of Bax and cleaved caspase-3.

Conclusions: Our results suggest that PQQ can protect rat NP cells against oxidative stress via a mitochondria-mediated pathway. PQQ might be useful as a potential pharmaceutical agent in the prevention of intervertebral disc degeneration.

Citing Articles

Custom-Made Ce-Mn Bimetallic Nanozyme for the Treatment of Intervertebral Disc Degeneration by Inhibiting Oxidative Stress and Modulating Macrophage M1/M2 Polarization.

Wu J, Chen Z, Huang H, Wang H, Wang X, Lu Z Biomater Res. 2024; 28:0118.

PMID: 39717477 PMC: 11665849. DOI: 10.34133/bmr.0118.

Tetrahedral framework nucleic acids-based delivery of microRNA-155 alleviates intervertebral disc degeneration through targeting Bcl-2/Bax apoptosis pathway.

Li Z, Tang Y, Wang L, Wang K, Huang S, Chen Y Cell Prolif. 2024; 57(11):e13689.

PMID: 38899529 PMC: 11533059. DOI: 10.1111/cpr.13689.

N-cadherin Alleviates Apoptosis and Senescence of Nucleus Pulposus Cells via Suppressing ROS-dependent ERS in the Hyper-osmolarity Microenvironment.

Zou L, Wang Y, Hu Y, Liu L, Luo L, Chen Z Int J Med Sci. 2024; 21(2):341-356.

PMID: 38169592 PMC: 10758147. DOI: 10.7150/ijms.90591.

The Pivotal Role of Nrf2 Signal Axis in Intervertebral Disc Degeneration.

Pan C, Hou W, Deng X, Liu J, Chi R, Shang X J Inflamm Res. 2023; 16:5819-5833.

PMID: 38076332 PMC: 10710182. DOI: 10.2147/JIR.S432575.

Rescuing Nucleus Pulposus Cells From Senescence via Dual-Functional Greigite Nanozyme to Alleviate Intervertebral Disc Degeneration.

Shi Y, Li H, Chu D, Lin W, Wang X, Wu Y Adv Sci (Weinh). 2023; 10(25):e2300988.

PMID: 37400370 PMC: 10477883. DOI: 10.1002/advs.202300988.

References

Hobara N, Watanabe A, Kobayashi M, Tsuji T, Gomita Y, Araki Y . Quinone derivatives lower blood and liver acetaldehyde but not ethanol concentrations following ethanol loading to rats. Pharmacology. 1988; 37(4):264-7. DOI: 10.1159/000138475. View

Park E, Park J . High glucose-induced oxidative stress promotes autophagy through mitochondrial damage in rat notochordal cells. Int Orthop. 2013; 37(12):2507-14. PMC: 3843215. DOI: 10.1007/s00264-013-2037-8. View

Shankar B, Pandey R, Amin P, Misra H, Sainis K . Role of glutathione in augmenting the anticancer activity of pyrroloquinoline quinone (PQQ). Redox Rep. 2010; 15(4):146-54. PMC: 7067314. DOI: 10.1179/174329210X12650506623762. View

Zhang Q, Shen M, Ding M, Shen D, Ding F . The neuroprotective action of pyrroloquinoline quinone against glutamate-induced apoptosis in hippocampal neurons is mediated through the activation of PI3K/Akt pathway. Toxicol Appl Pharmacol. 2011; 252(1):62-72. DOI: 10.1016/j.taap.2011.02.006. View

Xiong X, Zhao Y, Ge X, Yuan S, Wang J, Zhi J . Production and radioprotective effects of pyrroloquinoline quinone. Int J Mol Sci. 2012; 12(12):8913-23. PMC: 3257108. DOI: 10.3390/ijms12128913. View

Xu F, Yu H, Liu J, Cheng L . Pyrroloquinoline quinone inhibits oxygen/glucose deprivation-induced apoptosis by activating the PI3K/AKT pathway in cardiomyocytes. Mol Cell Biochem. 2013; 386(1-2):107-15. DOI: 10.1007/s11010-013-1849-6. View

Wei A, Brisby H, Chung S, Diwan A . Bone morphogenetic protein-7 protects human intervertebral disc cells in vitro from apoptosis. Spine J. 2007; 8(3):466-74. DOI: 10.1016/j.spinee.2007.04.021. View

Roberts S, Evans H, Trivedi J, Menage J . Histology and pathology of the human intervertebral disc. J Bone Joint Surg Am. 2006; 88 Suppl 2:10-4. DOI: 10.2106/JBJS.F.00019. View

Kim K, Ha K, Lee J, Rhyu K, An H, Woo Y . The apoptotic effects of oxidative stress and antiapoptotic effects of caspase inhibitors on rat notochordal cells. Spine (Phila Pa 1976). 2007; 32(22):2443-8. DOI: 10.1097/BRS.0b013e318157395a. View

10.

Cheng Y, Yang S, Lin F . Thermosensitive chitosan-gelatin-glycerol phosphate hydrogel as a controlled release system of ferulic acid for nucleus pulposus regeneration. Biomaterials. 2011; 32(29):6953-61. DOI: 10.1016/j.biomaterials.2011.03.065. View

11.

Min Z, Wang L, Jin J, Wang X, Zhu B, Chen H . Pyrroloquinoline Quinone Induces Cancer Cell Apoptosis via Mitochondrial-Dependent Pathway and Down-Regulating Cellular Bcl-2 Protein Expression. J Cancer. 2014; 5(7):609-24. PMC: 4143536. DOI: 10.7150/jca.9002. View

12.

Nasto L, Robinson A, Ngo K, Clauson C, Dong Q, St Croix C . Mitochondrial-derived reactive oxygen species (ROS) play a causal role in aging-related intervertebral disc degeneration. J Orthop Res. 2013; 31(7):1150-7. PMC: 3668354. DOI: 10.1002/jor.22320. View

13.

Li X, Phillips F, An H, Ellman M, Thonar E, Wu W . The action of resveratrol, a phytoestrogen found in grapes, on the intervertebral disc. Spine (Phila Pa 1976). 2008; 33(24):2586-95. PMC: 2905225. DOI: 10.1097/BRS.0b013e3181883883. View

14.

Tao R, Karliner J, Simonis U, Zheng J, Zhang J, Honbo N . Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 2007; 363(2):257-62. PMC: 2844438. DOI: 10.1016/j.bbrc.2007.08.041. View

15.

Rodriguez E, Roughley P . Link protein can retard the degradation of hyaluronan in proteoglycan aggregates. Osteoarthritis Cartilage. 2006; 14(8):823-9. DOI: 10.1016/j.joca.2006.02.008. View

16.

Ye J, Li J, Yu Y, Wei Q, Deng W, Yu L . L-carnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway. Regul Pept. 2010; 161(1-3):58-66. DOI: 10.1016/j.regpep.2009.12.024. View

17.

Wai E, Roffey D, Bishop P, Kwon B, Dagenais S . Causal assessment of occupational lifting and low back pain: results of a systematic review. Spine J. 2010; 10(6):554-66. DOI: 10.1016/j.spinee.2010.03.033. View

18.

Poveda L, Hottiger M, Boos N, Wuertz K . Peroxynitrite induces gene expression in intervertebral disc cells. Spine (Phila Pa 1976). 2009; 34(11):1127-33. DOI: 10.1097/BRS.0b013e31819f2330. View

19.

Rahman M, Kim N, Yang H, Huh S . Angelicin induces apoptosis through intrinsic caspase-dependent pathway in human SH-SY5Y neuroblastoma cells. Mol Cell Biochem. 2012; 369(1-2):95-104. DOI: 10.1007/s11010-012-1372-1. View

20.

Ali R, Le Maitre C, Richardson S, Hoyland J, Freemont A . Connective tissue growth factor expression in human intervertebral disc: implications for angiogenesis in intervertebral disc degeneration. Biotech Histochem. 2008; 83(5):239-45. DOI: 10.1080/10520290802539186. View