The mitochondrial antioxidant SS-31 attenuated lipopolysaccharide-induced apoptosis and pyroptosis of nucleus pulposus cells via scavenging mitochondrial ROS and maintaining the stability of mitochondrial dynamics

References

• Modic MT, Ross JS. Lumbar degenerative disk disease. Radiology. 2007;245(1):43–61.
   PubMed Web of Science ®Google Scholar
• Nishida K, Doita M, Takada T, et al. [Biological approach for treatment of degenerative disc diseases]. Clinical Calcium. 2005;15(3):79–86.
   PubMedGoogle Scholar
• Biyani A, Andersson GB. Low back pain: pathophysiology and management. J Am Acad Orthop Surg. 2004;12(2):106–115.
   PubMed Web of Science ®Google Scholar
• Zhang GZ, Deng YJ, Xie QQ, et al. Sirtuins and intervertebral disc degeneration: Roles in inflammation, oxidative stress, and mitochondrial function. Clin Chim Acta. 2020;508:33–42.
   PubMed Web of Science ®Google Scholar
• Molinos M, Almeida CR, Caldeira J, et al. Inflammation in intervertebral disc degeneration and regeneration. J R Soc Interface. 2015;12(104):20141191.
   PubMed Web of Science ®Google Scholar
• Chen D, Xia D, Pan Z, et al. Metformin protects against apoptosis and senescence in nucleus pulposus cells and ameliorates disc degeneration in vivo. Cell Death Dis. 2016;7(10):e2441.
   PubMedGoogle Scholar
• Bai Z, Liu W, He D, et al. Protective effects of autophagy and NFE2L2 on reactive oxygen species-induced pyroptosis of human nucleus pulposus cells. Aging (Albany NY)). 2020;12(8):7534–7548.
   PubMedGoogle Scholar
• Zhang HJ, Ma XH, Xie SL, et al. Knockdown of miR-660 protects nucleus pulposus cells from TNF-a-induced apoptosis by targeting serum amyloid A1. J Orthop Surg Res. 2020;15(1):7.
   PubMed Web of Science ®Google Scholar
• Cosamalón-Gan I, Cosamalón-Gan T, Mattos-Piaggio G, et al. Inflammation in the intervertebral disc herniation. Neurocirugia (English Edition). 2021;32(1):21–35.
   PubMedGoogle Scholar
• Wang Y, Che M, Xin J, et al. The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomed Pharmacother. 2020;131:110660.
   PubMed Web of Science ®Google Scholar
• Wei K, Dai J, Wang Z, et al. Oxymatrine suppresses IL-1β-induced degradation of the nucleus pulposus cell and extracellular matrix through the TLR4/NF-κB signaling pathway. Exp Biol Med (Maywood)). 2020;245(6):532–541.
   PubMed Web of Science ®Google Scholar
• Lin J, Chen J, Zhang Z, et al. Luteoloside inhibits IL-1β-induced apoptosis and catabolism in nucleus pulposus cells and ameliorates intervertebral disk degeneration. Front Pharmacol. 2019;10:868.
   PubMed Web of Science ®Google Scholar
• Jeong SY, Seol DW. The role of mitochondria in apoptosis. BMB Rep. 2008;41(1):11–22.
   PubMed Web of Science ®Google Scholar
• Green DR, Galluzzi L, Kroemer G. Mitochondria and the autophagy-inflammation-cell death axis in organismal aging. Science. 2011;333(6046):1109–1112.
   PubMed Web of Science ®Google Scholar
• Zhou R, Yazdi AS, Menu P, et al. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469(7329):221–225.
   PubMed Web of Science ®Google Scholar
• Banoth B, Cassel SL. Mitochondria in innate immune signaling. Transl Res. 2018;202:52–68.
   PubMed Web of Science ®Google Scholar
• Kang L, Liu S, Li J, et al. The mitochondria-targeted anti-oxidant MitoQ protects against intervertebral disc degeneration by ameliorating mitochondrial dysfunction and redox imbalance. Cell Prolif. 2020;53(3):e12779.
   PubMed Web of Science ®Google Scholar
• Song Y, Lu S, Geng W, et al. Mitochondrial quality control in intervertebral disc degeneration. Exp Mol Med. 2021;53(7):1124–1133.
   PubMed Web of Science ®Google Scholar
• Dandekar A, Mendez R, Zhang K. Cross talk between ER stress, oxidative stress, and inflammation in health and disease. Methods Molecul Biol (Clifton, NJ. ). 2015;1292:205–214.
   PubMedGoogle Scholar
• El Assar M, Angulo J, Rodríguez-Mañas L. Oxidative stress and vascular inflammation in aging. Free Radic Biol Med. 2013;65:380–401.
   PubMed Web of Science ®Google Scholar
• Amaral EP, Vinhaes CL, Oliveira-de-Souza D, et al. The interplay between systemic inflammation, oxidative stress, and tissue remodeling in tuberculosis. Antioxid Redox Signal. 2021;34(6):471–485.
   PubMed Web of Science ®Google Scholar
• van Horssen J, van Schaik P, Witte M. Inflammation and mitochondrial dysfunction: a vicious circle in neurodegenerative disorders? Neurosci Lett. 2019;710:132931.
   PubMed Web of Science ®Google Scholar
• Kelley N, Jeltema D, Duan Y, et al. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. IJMS. 2019;20(13):3328.
   Google Scholar
• Gong Z, Pan J, Shen Q, et al. Mitochondrial dysfunction induces NLRP3 inflammasome activation during cerebral ischemia/reperfusion injury. J Neuroinflammation. 2018;15(1):242.
   PubMedGoogle Scholar
• Hoseini Z, Sepahvand F, Rashidi B, et al. NLRP3 inflammasome: Its regulation and involvement in atherosclerosis. J Cell Physiol. 2018;233(3):2116–2132.
   PubMed Web of Science ®Google Scholar
• Chen X, Liu G, Yuan Y, et al. NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF-κB signaling. Cell Death Dis. 2019;10(12):906.
   PubMedGoogle Scholar
• Feng H, Mou SQ, Li WJ, et al. Resveratrol inhibits ischemia-induced myocardial senescence signals and NLRP3 inflammasome activation. Oxid Med Cell Longev. 2020;2020:2647807.
   PubMed Web of Science ®Google Scholar
• Zhong X, Liu M, Yao W, et al. Epigallocatechin-3-gallate attenuates microglial inflammation and neurotoxicity by suppressing the activation of canonical and noncanonical inflammasome via TLR4/NF-κB pathway. Mol Nutr Food Res. 2019;63(21):e1801230.
   PubMed Web of Science ®Google Scholar
• Zhang C, Wang X, Nie G, et al. In vivo assessment of molybdenum and cadmium co-induce nephrotoxicity via NLRP3/caspase-1-mediated pyroptosis in ducks. J Inorg Biochem. 2021;224:111584.
   PubMed Web of Science ®Google Scholar
• Chavez JD, Tang X, Campbell MD, et al. Mitochondrial protein interaction landscape of SS-31. Proc Natl Acad Sci USA. 2020;117(26):15363–15373.
   PubMed Web of Science ®Google Scholar
• Escribano-Lopez I, Diaz-Morales N, Iannantuoni F, et al. The mitochondrial antioxidant SS-31 increases SIRT1 levels and ameliorates inflammation, oxidative stress and leukocyte-endothelium interactions in type 2 diabetes. Sci Rep. 2018;8(1):15862.
   PubMedGoogle Scholar
• Liu Y, Yang W, Sun X, et al. SS31 ameliorates sepsis-induced heart injury by inhibiting oxidative stress and inflammation. Inflammation. 2019;42(6):2170–2180.
   PubMed Web of Science ®Google Scholar
• Liu Y, Fu H, Wu Y, et al. Elamipretide (SS-31) improves functional connectivity in hippocampus and other related regions following prolonged neuroinflammation induced by lipopolysaccharide in aged rats. Front Aging Neurosci. 2021;13:600484.
   PubMed Web of Science ®Google Scholar
• Zhao K, An R, Xiang Q, et al. Acid-sensing ion channels regulate nucleus pulposus cell inflammation and pyroptosis via the NLRP3 inflammasome in intervertebral disc degeneration. Cell Prolif. 2021;54(1):e12941.
   PubMed Web of Science ®Google Scholar
• Huang Y, Peng Y, Sun J, et al. Nicotinamide phosphoribosyl transferase controls NLRP3 inflammasome activity through MAPK and NF-κB signaling in nucleus pulposus cells, as suppressed by melatonin. Inflammation. 2020;43(3):796–809.
   PubMed Web of Science ®Google Scholar
• Chen F, Jiang G, Liu H, et al. Melatonin alleviates intervertebral disc degeneration by disrupting the IL-1β/NF-κB-NLRP3 inflammasome positive feedback loop. Bone Res. 2020;8:10.
   PubMed Web of Science ®Google Scholar
• Cai J, Jiang Y, Zhang M, et al. Protective effects of mitochondrion-targeted peptide SS-31 against hind limb ischemia-reperfusion injury. J Physiol Biochem. 2018;74(2):335–343.
   PubMed Web of Science ®Google Scholar
• Szeto HH, Liu S, Soong Y, et al. Protection of mitochondria prevents high-fat diet-induced glomerulopathy and proximal tubular injury. Kidney Int. 2016;90(5):997–1011.
   PubMed Web of Science ®Google Scholar
• Tian Y, Bao Z, Ji Y, et al. Epigallocatechin-3-gallate protects H2O2-induced nucleus pulposus cell apoptosis and inflammation by inhibiting cGAS/Sting/NLRP3 activation. Drug Des Devel Ther. 2020;14:2113–2122.
   PubMed Web of Science ®Google Scholar
• Zhao W, Xu Z, Cao J, et al. Elamipretide (SS-31) improves mitochondrial dysfunction, synaptic and memory impairment induced by lipopolysaccharide in mice. J Neuroinflammation. 2019;16(1):230.
   PubMed Web of Science ®Google Scholar
• Peng X, Zhang C, Bao JP, et al. A20 of nucleus pulposus cells plays a self-protection role via the nuclear factor-kappa B pathway in the inflammatory microenvironment. Bone Joint Res. 2020;9(5):225–235.
   PubMed Web of Science ®Google Scholar
• Liu Y, Lin J, Wu X, et al. Aspirin-Mediated attenuation of intervertebral disc degeneration by ameliorating reactive oxygen species in vivo and in vitro. Oxid Med Cell Longev. 2019;2019:7189854.
   PubMed Web of Science ®Google Scholar
• Cadenas S. Mitochondrial uncoupling, ROS generation and cardioprotection. Biochim Biophys Acta Bioenerg. 2018;1859(9):940–950.
   PubMed Web of Science ®Google Scholar
• Bagkos G, Koufopoulos K, Piperi C. A new model for mitochondrial membrane potential production and storage. Med Hypotheses. 2014;83(2):175–181.
   PubMed Web of Science ®Google Scholar
• Eisner V, Picard M, Hajnóczky G. Mitochondrial dynamics in adaptive and maladaptive cellular stress responses. Nat Cell Biol. 2018;20(7):755–765.
   PubMed Web of Science ®Google Scholar
• Arioz BI, Tastan B, Tarakcioglu E, et al. Melatonin attenuates LPS-Induced acute Depressive-like behaviors and microglial NLRP3 inflammasome activation through the SIRT1/Nrf2 pathway. Front Immunol. 2019;10:1511.
   PubMed Web of Science ®Google Scholar
• Swanson KV, Deng M, Ting JP. The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol. 2019;19(8):477–489.
   PubMed Web of Science ®Google Scholar
• Shao BZ, Xu ZQ, Han BZ, et al. NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol. 2015;6:262.
   PubMed Web of Science ®Google Scholar
• Navone SE, Marfia G, Giannoni A, et al. Inflammatory mediators and signalling pathways controlling intervertebral disc degeneration. Histol Histopathol. 2017;32(6):523–542.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Yang J, Zhou X, et al. Knockdown of miR-222 inhibits inflammation and the apoptosis of LPS-stimulated human intervertebral disc nucleus pulposus cells. Int J Mol Med. 2019;44(4):1357–1365.
   PubMed Web of Science ®Google Scholar
• Rajan NE, Bloom O, Maidhof R, et al. Toll-Like receptor 4 (TLR4) expression and stimulation in a model of intervertebral disc inflammation and degeneration. Spine. 2013;38(16):1343–1351.
   PubMed Web of Science ®Google Scholar
• Ma Z, Wang D, Weng J, et al. BNIP3 decreases the LPS-induced inflammation and apoptosis of chondrocytes by promoting the development of autophagy. J Orthop Surg Res. 2020;15(1):284.
   PubMed Web of Science ®Google Scholar
• Vergroesen PP, Kingma I, Emanuel KS, et al. Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthr Cartil. 2015;23(7):1057–1070.
   PubMed Web of Science ®Google Scholar
• Chen ZB, Yu YB, Wa QB, et al. The role of quinazoline in ameliorating intervertebral disc degeneration by inhibiting oxidative stress and anti-inflammation via NF-κB/MAPKs signaling pathway. Eur Rev Med Pharmacol Sci. 2020;24(4):2077–2086.
   PubMed Web of Science ®Google Scholar
• Szeto HH, Liu S, Soong Y, et al. Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury. J Am Soc Nephrol. 2011;22(6):1041–1052.
   PubMed Web of Science ®Google Scholar
• Thoma A, Akter-Miah T, Reade RL, et al. Targeting reactive oxygen species (ROS) to combat the age-related loss of muscle mass and function. Biogerontology. 2020;21(4):475–484.
   PubMed Web of Science ®Google Scholar
• Mo Y, Deng S, Zhang L, et al. SS-31 reduces inflammation and oxidative stress through the inhibition of Fis1 expression in lipopolysaccharide-stimulated microglia. Biochem Biophys Res Commun. 2019;520(1):171–178.
   PubMed Web of Science ®Google Scholar
• Thomas DA, Stauffer C, Zhao K, et al. Mitochondrial targeting with antioxidant peptide SS-31 prevents mitochondrial depolarization, reduces islet cell apoptosis, increases islet cell yield, and improves posttransplantation function. J Am Soc Nephrol. 2007;18(1):213–222.
   PubMed Web of Science ®Google Scholar
• Blanco FJ, Fernández-Moreno M. Mitochondrial biogenesis: a potential therapeutic target for osteoarthritis. Osteoarthr Cartil. 2020;28(8):1003–1006.
   PubMed Web of Science ®Google Scholar
• Chen ZH, Jin SH, Wang MY, et al. Enhanced NLRP3, caspase-1, and IL- 1β levels in degenerate human intervertebral disc and their association with the grades of disc degeneration. Anat Rec (Hoboken)). 2015;298(4):720–726.
   PubMedGoogle Scholar