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The protective effect of nicotinamide riboside on mitochondrial function of retinal ganglion cell

Published on Feb. 08, 2024Total Views: 1054 times Total Downloads: 1132 times Download Mobile

Author: DENG Xizhi ZHANG Nan ZENG Wen ZHU Min ZHANG Pengyu LI Fang JIANG Bin KE Min

Affiliation: Department of Ophthalmology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China

Keywords: Nicotinamide riboside Mitochondria Oxidative stress Optic nerve protection

DOI: 10.12173/j.issn.1008-049X.202401119

Reference: DENG Xizhi, ZHANG Nan , ZENG Wen, ZHU Min, ZHANG Pengyu, LI Fang, JIANG Bin, KE Min.The protective effect of nicotinamide riboside on mitochondrial function of retinal ganglion cell[J].Zhongguo Yaoshi Zazhi,2024, 27(1):1-7.DOI: 10.12173/j.issn.1008-049X.202401119.[Article in Chinese]

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Abstract

Objective  To explore the protective effect in a model of nicotinamide riboside (NR) against carbonyl cyanide m-chlorophenylhydrazone (CCCP)-induced oxidative stress in R28 cells.

Methods  4 μmol/L CCCP was used to induce oxidative stress in R28 cells, and 400 nmol/L NR was used to intervene. The cell viability was quantified by CCK-8 assay. The apoptosis was detected by Annexin-V/PI double staining and flow cytometry. Western blotting was used to examine the levels of Cytochrome C, Caspase-3, and Caspase-9 to evaluate the apoptosis. Tetramethylrhodamine ethyl ester was used to detect the mitochondrial membrane potential (MMP), MitoSOX was used to detect the mitochondrial reactive oxygen species (mtROS) levels, and adenosine triphosphate (ATP) assay kit was used to assess ATP generation ability to evaluate mitochondrial function.

Results  After CCCP treatment of R28 cells, the cell viability decreased, the apoptotic protein levels and apoptosis rates increased, the MMP decreased, and the mtROS generation increased (P﹤0.05). After NR pretreatment, the cell viability increased, the apoptotic protein levels and apoptosis rates decreased, the MMP increased, and the mtROS generation decreased (P﹤0.05).

Conclusion: NR enhances the cell viability, reduces the expression of apoptotic proteins, and ultimately reduces the apoptosis of retinal ganglion cell by inhibiting oxidative stress response and protecting mitochondrial function.

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References

1.Carrero L, Antequera D, Alcalde I, et al. Disturbed circadian rhythm and retinal degeneration in a mouse model of Alzheimer's disease[J]. Acta Neuropathol Commun, 2023, 11(1): 55. DOI: 10.1186/s40478-023-01529-6.

2.Clark AF. The cell and molecular biology of glaucoma: biomechanical factors in glaucoma[J]. Invest Ophthalmol Vis Sci, 2012, 53(5): 2473-2475. DOI: 10.1167/iovs.12-9483g. DOI: 10.1167/iovs.12-9483g.

3.Adornetto A, Rombola L, Morrone LA, et al. Natural products: evidence for neuroprotection to be exploited in glaucoma[J]. Nutrients, 2020, 12(10): 3158. DOI: 10.3390/nu12103158.

4.Lin WJ, Kuang HY. Oxidative stress induces autophagy in response to multiple noxious stimuli in retinal ganglion cells[J]. Autophagy, 2014, 10(10): 1692-1701. DOI: 10.4161/auto.36076.

5.Osborne NN, Del Olmo-Aguado S. Maintenance of retinal ganglion cell mitochondrial functions as a neuroprotective strategy in glaucoma[J]. Curr Opin Pharmacol, 2013, 13(1): 16-22. DOI: 10.1016/j.coph.2012.09.002.

6.Chrysostomou V, Rezania F, Trounce IA, et al. Oxidative stress and mitochondrial dysfunction in glaucoma[J]. Curr Opin Pharmacol, 2013, 13(1): 12-15. DOI: 10.1016/j.coph.2012.09.008.

7.Damgaard MV, Treebak JT. What is really known about the effects of nicotinamide riboside supplementation in humans[J]. Sci Adv, 2023, 9(29): eadi4862. DOI: 10.1126/sciadv.adi4862.

8.Rajman L, Chwalek K, SInclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence[J]. Cell Metab, 2018, 27(3): 529-547. DOI: 10.1016/j.cmet.2018. 02.011.

9.Seigel GM. Review: R28 retinal precursor cells: the first 20 years[J]. Mol Vis, 2014, 20: 301-306. https://pubmed.ncbi.nlm.nih.gov/24644404/.

10.Ashok A, Singh N, Chaudhary S, et al. Retinal degeneration and Alzheimer's disease: an evolving link[J]. Int J Mol Sci, 2020, 21(19): 7290. DOI: 10.3390/ijms21197290.

11.Kuang G, Halimitabrizi M, Edziah AA, et al. The potential for mitochondrial therapeutics in the treatment of primary open-angle glaucoma: a review[J]. Front Physiol, 2023, 14: 1184060. DOI: 10.3389/fphys.2023.1184060.

12.Catalani E, Brunetti K, Del Quondam S, et al. Targeting mitochondrial dysfunction and oxidative stress to prevent the neurodegeneration of retinal ganglion cells[J]. Antioxidants (Basel), 2023, 12(11): 2011. DOI: 10.3390/antiox12112011.

13.Lenaers G, Neutzner A, Le Dantec Y, et al. Dominant optic atrophy: culprit mitochondria in the optic nerve[J]. Prog Retin Eye Res, 2021, 83: 100935. DOI: 10.1016/j.preteyeres.2020.100935.

14.Domenech EB, Marfany E. The relevance of oxidative stress in the pathogenesis and therapy of retinal dystrophies[J]. Antioxidants (Basel), 2020, 9(4): 347. DOI: 10.3390/antiox9040347

15.Sim RH, Sirasanagandla SR, Das S, et al. Treatment of glaucoma with natural products and their mechanism of action: an update[J]. Nutrients, 2022, 14(3): 534. DOI: 10.3390/nu14030534.

16.Nascimento-Dos-Santos G, De-Souza-Ferreira E, Lani R, et al. Neuroprotection from optic nerve injury and modulation of oxidative metabolism by transplantation of active mitochondria to the retina[J]. Biochim Biophys Acta Mol Basis Dis, 2020, 1866(5): 165686. DOI: 10.1016/j.bbadis.2020.165686.

17.Amato R, Catalani E, Dal Monte M, et al. Morpho-functional analysis of the early changes induced in retinal ganglion cells by the onset of diabetic retinopathy: The effects of a neuroprotective strategy[J]. Pharmacol Res, 2022, 185: 106516. DOI: 10.1016/j.phrs.2022.106516.

18.Ju WK, Perkins GA, Kim KY, et al. Glaucomatous optic neuropathy: mitochondrial dynamics, dysfunction and protection in retinal ganglion cells[J]. Prog Retin Eye Res, 2023, 95: 101136. DOI: 10.1016/j.preteyeres.2022.101136.

19.Cercillieux A, Ciarlo E, Canto C. Balancing NAD+ deficits with nicotinamide riboside: therapeutic possibilities and limitations[J]. Cell Mol Life Sci, 2022, 79(8): 463. DOI: 10.1007/s00018-022-04499-5.

20.Zhang X, Zhang N, Chrenek MA, et al. Systemic treatment with nicotinamide riboside is protective in two mouse models of retinal ganglion cell damage[J]. Pharmaceutics, 2021, 13(6): 893. DOI: 10.3390/pharmaceutics13060893.

21.Leung CKS, Ren ST, Chan PPM, et al. Nicotinamide riboside as a neuroprotective therapy for glaucoma: study protocol for a randomized, double-blind, placebo-control trial[J]. Trials, 2022, 23(1): 45. DOI: 10.1186/s13063-021-05968-1.

22.Hou YJ, Wei Y, Lautrup S, et al. NAD+ supplementation reduces neuroinflammation and cell senescence in a transgenic mouse model of Alzheimer's disease via cGAS-STING[J]. Proc Natl Acad Sci U S A, 2021, 118(37): e2011226118. DOI: 10.1073/pnas.2011226118.

23.Wang S, Wan T, Ye M, et al. Nicotinamide riboside attenuates alcohol induced liver injuries via activation of SirT1/PGC-1alpha/mitochondrial biosynthesis pathway[J]. Redox Biol, 2018, 17: 89-98. DOI: 10.1016/j.redox.2018.04.006.

24.Zhou B, Wang DD, Qiu Y, et al. Boosting NAD level suppresses inflammatory activation of PBMCs in heart failure[J]. J Clin Invest, 2020, 130(11): 6054-6063. DOI: 10.1172/JCI138538.

25.Trammell SA, Schmidt MS, Weidemann BJ, et al. Nicotinamide riboside is uniquely and orally bioavailable in mice and humans[J]. Nat Commun, 2016, 7: 12948. DOI: 10.1038/ncomms12948.

26.Martens CR, Denman BA, Mazzo MR, et al. Chronic nicotinamide riboside supplementation is well-tolerated and elevates NAD+ in healthy middle-aged and older adults[J]. Nat Commun, 2018, 9(1): 1286. DOI: 10.1038/s41467-018-03421-7.

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