Login Register Cart 0
Generic placeholder image

当代阿耳茨海默病研究

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in English
Research Article

党参多糖通过CD38/NAD+信号通路缓解Aβ1-40诱导的PC12细胞能量代谢紊乱

卷 18, 期 3, 2021

发表于: 23 September, 2021

页: [208 - 221] 页: 14

弟呕挨: 10.2174/1567205018666210608103831

open access plus

摘要

背景：阿尔茨海默氏症(AD)是最常见的痴呆症类型，具有复杂的发病机制，没有有效的治疗方法。能量代谢紊乱作为AD的早期病理事件，作为AD的一个很有前途的研究领域，已经引起了人们的关注。党参多糖是党参的主要有效成分，已被证明可以调节能量代谢。 方法：为进一步研究党参多糖在AD中的作用和作用机制，本研究采用Aβ1-40诱导的PC12细胞模型，研究了党参多糖的保护作用及其改善能量代谢功能障碍的潜在机制。 结果：结果显示，Aβ1-40诱导PC12细胞活力、能量代谢分子(ATP、NAD+、NAD+/NADH)和线粒体膜电位(MMP)降低，ROS升高。此外，研究发现Aβ1-40增加了与NAD+稳态相关的CD38表达，而沉默信息调控2同源物1(SIRT1，SIRT3)、过氧化物酶体增殖物激活受体γ共激活因子1-α(PGC-1α)和SIRT3活性降低。党参多糖增加了与NAD+相关的NAD+、NAD+/NADH、SIRT3、SIRT1和PGC-1α，从而部分恢复了ATP。 结论：党参多糖的研究结果显示，党参多糖可以保护PC12细胞免受Aβ1-40诱导的损伤，提示党参的这些成分可能是AD患者的早期治疗选择。

关键词: 阿尔茨海默病、能量代谢障碍、党参多糖、NAD+、CD38、神经原纤维缠结。

« Previous Next »
[1]
Hampel H, Mesulam MM, Cuello AC, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain 2018; 141(7): 1917-33.
[http://dx.doi.org/10.1093/brain/awy132] [PMID: 29850777]
[2]
Yin F, Sancheti H, Patil I, Cadenas E. Energy metabolism and inflammation in brain aging and Alzheimer’s disease. Free Radic Biol Med 2016; 100: 108-22.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.04.200] [PMID: 27154981]
[3]
Rijpma A, van der Graaf M, Meulenbroek O, Olde Rikkert MGM, Heerschap A. Altered brain high-energy phosphate metabolism in mild Alzheimer’s disease: A 3-dimensional 31P MR spectroscopic imaging study. Neuroimage Clin 2018; 18: 254-61.
[http://dx.doi.org/10.1016/j.nicl.2018.01.031] [PMID: 29876246]
[4]
Xiao W, Wang RS, Handy DE, Loscalzo J. NAD(H) and NADP(H) redox couples and cellular energy metabolism. Antioxid Redox Signal 2018; 28(3): 251-72.
[http://dx.doi.org/10.1089/ars.2017.7216] [PMID: 28648096]
[5]
Hou Y, Lautrup S, Cordonnier S, et al. NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc Natl Acad Sci USA 2018; 115(8): E1876-85.
[http://dx.doi.org/10.1073/pnas.1718819115] [PMID: 29432159]
[6]
Yang Y, Sauve AA. NAD(+) metabolism: Bioenergetics, signaling and manipulation for therapy. Biochim Biophys Acta 2016; 1864(12): 1787-800.
[http://dx.doi.org/10.1016/j.bbapap.2016.06.014] [PMID: 27374990]
[7]
Chini CCS, Tarragó MG, Chini EN. NAD and the aging process: Role in life, death and everything in between. Mol Cell Endocrinol 2017; 455: 62-74.
[http://dx.doi.org/10.1016/j.mce.2016.11.003] [PMID: 27825999]
[8]
Rajman L, Chwalek K, Sinclair DA. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab 2018; 27(3): 529-47.
[http://dx.doi.org/10.1016/j.cmet.2018.02.011] [PMID: 29514064]
[9]
Katsyuba E, Auwerx J. Modulating NAD+ metabolism, from bench to bedside. EMBO J 2017; 36(18): 2670-83.
[http://dx.doi.org/10.15252/embj.201797135] [PMID: 28784597]
[10]
Chini EN, Chini CCS, Espindola Netto JM, de Oliveira GC, van Schooten W. The pharmacology of CD38/nadase: An emerging target in cancer and diseases of aging. Trends Pharmacol Sci 2018; 39(4): 424-36.
[http://dx.doi.org/10.1016/j.tips.2018.02.001] [PMID: 29482842]
[11]
Ting KY, Leung CF, Graeff RM, Lee HC, Hao Q, Kotaka M. Porcine CD38 exhibits prominent secondary NAD(+) cyclase activity. Protein Sci 2016; 25(3): 650-61.
[http://dx.doi.org/10.1002/pro.2859] [PMID: 26660500]
[12]
Hogan KA, Chini CCS, Chini EN. The multi-faceted ecto-enzyme CD38: Roles in immunomodulation, cancer, aging, and metabolic diseases. Front Immunol 2019; 10: 1187.
[http://dx.doi.org/10.3389/fimmu.2019.01187] [PMID: 31214171]
[13]
Jiang Y, Liu Y, Guo Q, et al. Acetylenes and fatty acids from Codonopsis pilosula. Acta Pharm Sin B 2015; 5(3): 215-22.
[http://dx.doi.org/10.1016/j.apsb.2015.03.005] [PMID: 26579449]
[14]
Fu YP, Feng B, Zhu ZK, et al. The Polysaccharides from Codonopsis pilosula modulates the immunity and intestinal microbiota of cyclophosphamide-treated immunosuppressed mice. Molecules 2018; 23(7): 1801-14.
[http://dx.doi.org/10.3390/molecules23071801] [PMID: 30037030]
[15]
Weon JB, Eom MR, Jung YS, et al. Steamed and fermented ethanolic extract from codonopsis lanceolata attenuates amyloid-β-induced memory impairment in mice. Evid Based Complement Alternat Med 2016; 2016: 1473801.
[http://dx.doi.org/10.1155/2016/1473801] [PMID: 27313637]
[16]
Huang X, Xing S, Chen C, Yu Z, Chen J. Salidroside protects PC12 cells from Aβ1-40-induced cytotoxicity by regulating the nicotinamide phosphoribosyltransferase signaling pathway. Mol Med Rep 2017; 16(3): 2700-6.
[http://dx.doi.org/10.3892/mmr.2017.6931] [PMID: 28714019]
[17]
Ma R, Hu J, Huang C, Wang M, Xiang J, Li G. JAK2/STAT5/Bcl-xL signalling is essential for erythropoietin-mediated protection against apoptosis induced in PC12 cells by the amyloid β-peptide Aβ25-35. Br J Pharmacol 2014; 171(13): 3234-45.
[http://dx.doi.org/10.1111/bph.12672] [PMID: 24597613]
[18]
Tao L, Liu X, Da W, Tao Z, Zhu Y. Pycnogenol achieves neuroprotective effects in rats with spinal cord injury by stabilizing the mitochondrial membrane potential. Neurol Res 2020; 42(7): 597-604.
[http://dx.doi.org/10.1080/01616412.2020.1773610] [PMID: 32497471]
[19]
Hu YR, Xing SL, Chen C, Shen DZ, Chen JL. Tiaoxin Recipe, a Chinese herbal formula, inhibits microRNA-34a expression in the APPswe/PS1ΔE9 mouse model of Alzheimer’s disease. J Integr Med 2019; 17(6): 404-9.
[http://dx.doi.org/10.1016/j.joim.2019.09.002] [PMID: 31548147]
[20]
Wang Z, Xie J, Yang Y, et al. Sulfated Cyclocarya paliurus polysaccharides markedly attenuates inflammation and oxidative damage in lipopolysaccharide-treated macrophage cells and mice. Sci Rep 2017; 7: 40402-15.
[http://dx.doi.org/10.1038/srep40402] [PMID: 28094275]
[21]
Yuan S, Xu CY, Xia J, Feng YN, Zhang XF, Yan YY. Extraction of polysaccharides from Codonopsis pilosula by fermentation with response surface methodology. Food Sci Nutr 2020; 8(12): 6660-9.
[http://dx.doi.org/10.1002/fsn3.1958] [PMID: 33312549]
[22]
Zhang L, Hu Y, Duan X, et al. Characterization and antioxidant activities of polysaccharides from thirteen boletus mushrooms. Int J Biol Macromol 2018; 113: 1-7.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.02.084] [PMID: 29458100]
[23]
Yu M, Zang D, Xu Y, Meng J, Qian S. Protective effect of ISO-1 against advanced glycation end product aggravation of PC12 cell injury induced by Aβ1-40. Mol Med Rep 2019; 20(3): 2135-42.
[http://dx.doi.org/10.3892/mmr.2019.10483] [PMID: 31322215]
[24]
Davalli P, Mitic T, Caporali A, Lauriola A, D’Arca D. ROS, cell senescence, and novel molecular mechanisms in aging and age-related diseases. Oxid Med Cell Longev 2016; 2016: 3565127.
[http://dx.doi.org/10.1155/2016/3565127] [PMID: 27247702]
[25]
Brand MD, Orr AL, Perevoshchikova IV, Quinlan CL. The role of mitochondrial function and cellular bioenergetics in ageing and disease. Br J Dermatol 2013; 169(Suppl 2): 1-8.
[http://dx.doi.org/10.1111/bjd.12208]
[26]
Pehar M, Harlan BA, Killoy KM, et al. Nicotinamide adenine dinucleotide metabolism and neurodegeneration. Antioxid Redox Signal 2018; 28(18): 1652-68.
[http://dx.doi.org/10.1089/ars.2017.7145] [PMID: 28548540]
[27]
Verdin E. NAD+ in aging, metabolism, and neurodegeneration. Science 2015; 350(6265): 1208-13.
[http://dx.doi.org/10.1126/science.aac4854] [PMID: 26785480]
[28]
Liang WS, Reiman EM, Valla J, et al. Alzheimer’s disease is associated with reduced expression of energy metabolism genes in posterior cingulate neurons. Proc Natl Acad Sci USA 2008; 105(11): 4441-6.
[http://dx.doi.org/10.1073/pnas.0709259105] [PMID: 18332434]
[29]
Müller WEG, Wang S, Ackermann M, et al. Rebalancing β-amyloid-induced decrease of ATP level by amorphous nano/micro polyphosphate: Suppression of the neurotoxic effect of amyloid β-protein fragment 25-35. Int J Mol Sci 2017; 18(10): 2154-67.
[http://dx.doi.org/10.3390/ijms18102154] [PMID: 29035351]
[30]
Swerdlow RH. Mitochondria and mitochondrial cascades in Alzheimer’s disease. J Alzheimers Dis 2018; 62(3): 1403-16.
[http://dx.doi.org/10.3233/JAD-170585] [PMID: 29036828]
[31]
Camici M, Garcia-Gil M, Tozzi MG. The inside story of adenosine. Int J Mol Sci 2018; 19(3): 784-97.
[http://dx.doi.org/10.3390/ijms19030784] [PMID: 29522447]
[32]
Frenguelli BG. The purine salvage pathway and the restoration of cerebral atp: implications for brain slice physiology and brain injury. Neurochem Res 2019; 44(3): 661-75.
[http://dx.doi.org/10.1007/s11064-017-2386-6] [PMID: 28836168]
[33]
Guo L, Tian J, Du H. Mitochondrial dysfunction and synaptic transmission failure in Alzheimer’s disease. J Alzheimers Dis 2017; 57(4): 1071-86.
[http://dx.doi.org/10.3233/JAD-160702] [PMID: 27662318]
[34]
Manoharan S, Guillemin GJ, Abiramasundari RS, Essa MM, Akbar M, Akbar MD. The role of reactive oxygen species in the pathogenesis of Alzheimer’s dsease, Parkinson’s disease, and Huntington’s disease: A mini review. Oxid Med Cell Longev 2016; 2016: 8590578.
[http://dx.doi.org/10.1155/2016/8590578] [PMID: 28116038]
[35]
Kausar S, Wang F, Cui H. The role of mitochondria in reactive oxygen species generation and its implications for neurodegenerative diseases. Cells 2018; 7(12): 274-89.
[http://dx.doi.org/10.3390/cells7120274] [PMID: 30563029]
[36]
Lee YJ, Park KS, Nam HS, Cho MK, Lee SH. Apigenin causes necroptosis by inducing ROS accumulation, mitochondrial dysfunction, and ATP depletion in malignant mesothelioma cells. Korean J Physiol Pharmacol 2020; 24(6): 493-502.
[http://dx.doi.org/10.4196/kjpp.2020.24.6.493] [PMID: 33093271]
[37]
Hung CH, Cheng SS, Cheung YT, et al. A reciprocal relationship between reactive oxygen species and mitochondrial dynamics in neurodegeneration. Redox Biol 2018; 14: 7-19.
[http://dx.doi.org/10.1016/j.redox.2017.08.010] [PMID: 28837882]
[38]
Weidling I, Swerdlow RH. Mitochondrial dysfunction and stress responses in Alzheimer’s disease. Biology (Basel) 2019; 8(2): 39-52.
[http://dx.doi.org/10.3390/biology8020039] [PMID: 31083585]
[39]
Clement J, Wong M, Poljak A, Sachdev P, Braidy N. The plasma NAD+ metabolome is dysregulated in “normal” aging. Rejuvenation Res 2019; 22(2): 121-30.
[http://dx.doi.org/10.1089/rej.2018.2077] [PMID: 30124109]
[40]
Zhu Y, Zhao KK, Tong Y, et al. Exogenous NAD(+) decreases oxidative stress and protects H2O2-treated RPE cells against necrotic death through the up-regulation of autophagy. Sci Rep 2016; 6: 26322.
[http://dx.doi.org/10.1038/srep26322] [PMID: 27240523]
[41]
Cantó C, Menzies KJ, Auwerx J. NAD(+) Metabolism and the control of energy homeostasis: A balancing act between mitochondria and the nucleus. Cell Metab 2015; 22(1): 31-53.
[http://dx.doi.org/10.1016/j.cmet.2015.05.023] [PMID: 26118927]
[42]
Jokinen R, Pirnes-Karhu S, Pietiläinen KH, Pirinen E. Adipose tissue NAD+-homeostasis, sirtuins and poly(ADP-ribose) polymerases -important players in mitochondrial metabolism and metabolic health. Redox Biol 2017; 12: 246-63.
[http://dx.doi.org/10.1016/j.redox.2017.02.011] [PMID: 28279944]
[43]
Tsuda M, Fukushima A, Matsumoto J, et al. Protein acetylation in skeletal muscle mitochondria is involved in impaired fatty acid oxidation and exercise intolerance in heart failure. J Cachexia Sarcopenia Muscle 2018; 9(5): 844-59.
[http://dx.doi.org/10.1002/jcsm.12322] [PMID: 30168279]
[44]
Bradshaw PC. Cytoplasmic and mitochondrial NADPH-coupled redox systems in the regulation of aging. Nutrients 2019; 11(3): 504.
[http://dx.doi.org/10.3390/nu11030504] [PMID: 30818813]
[45]
Bonkowski MS, Sinclair DA. Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol 2016; 17(11): 679-90.
[http://dx.doi.org/10.1038/nrm.2016.93] [PMID: 27552971]
[46]
Grabowska W, Sikora E, Bielak-Zmijewska A. Sirtuins, a promising target in slowing down the ageing process. Biogerontology 2017; 18(4): 447-76.
[http://dx.doi.org/10.1007/s10522-017-9685-9] [PMID: 28258519]
[47]
Ye JS, Chen L, Lu YY, Lei SQ, Peng M, Xia ZY. SIRT3 activator honokiol ameliorates surgery/anesthesia-induced cognitive decline in mice through anti-oxidative stress and anti-inflammatory in hippocampus. CNS Neurosci Ther 2019; 25(3): 355-66.
[http://dx.doi.org/10.1111/cns.13053] [PMID: 30296006]
[48]
Zheng J, Shi L, Liang F, et al. Sirt3 ameliorates oxidative stress and mitochondrial dysfunction after intracerebral hemorrhage in diabetic rats. Front Neurosci 2018; 12: 414-26.
[http://dx.doi.org/10.3389/fnins.2018.00414] [PMID: 29970985]
[49]
Yin J, Nielsen M, Carcione T, Li S, Shi J. Apolipoprotein E regulates mitochondrial function through the PGC-1α-sirtuin 3 pathway. Aging (Albany NY) 2019; 11(23): 11148-56.
[http://dx.doi.org/10.18632/aging.102516] [PMID: 31808750]
[50]
Yu L, Gong B, Duan W, et al. Melatonin ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic rats by preserving mitochondrial function: role of AMPK-PGC-1α-SIRT3 signaling. Sci Rep 2017; 7: 41337.
[http://dx.doi.org/10.1038/srep41337] [PMID: 28120943]
[51]
Liu J, Li D, Zhang T, Tong Q, Ye RD, Lin L. SIRT3 protects hepatocytes from oxidative injury by enhancing ROS scavenging and mitochondrial integrity. Cell Death Dis 2017; 8(10): e3158.
[http://dx.doi.org/10.1038/cddis.2017.564] [PMID: 29072685]
[52]
Schultz MB, Sinclair DA. Why NAD(+) Declines during aging: It’s destroyed. Cell Metab 2016; 23(6): 965-6.
[http://dx.doi.org/10.1016/j.cmet.2016.05.022] [PMID: 27304496]
[53]
Camacho-Pereira J, Tarragó MG, Chini CCS, et al. CD38 dictates age-related nad Decline and mitochondrial dysfunction through an SIRT3-dependent mechanism. Cell Metab 2016; 23(6): 1127-39.
[http://dx.doi.org/10.1016/j.cmet.2016.05.006] [PMID: 27304511]
[54]
Morandi F, Horenstein AL, Costa F, Giuliani N, Pistoia V, Malavasi F. CD38: A target for immunotherapeutic approaches in multiple myeloma. Front Immunol 2018; 9: 2722-33.
[http://dx.doi.org/10.3389/fimmu.2018.02722] [PMID: 30546360]
[55]
Tarragó MG, Chini CCS, Kanamori KS, et al. A potent and specific CD38 inhibitor ameliorates age-related metabolic dysfunction by reversing tissue NAD+ decline. Cell Metab 2018; 27(5): 1081-1095.e10.
[http://dx.doi.org/10.1016/j.cmet.2018.03.016] [PMID: 29719225]
[56]
Chiang SH, Harrington WW, Luo G, et al. Genetic ablation of CD 38 protects against western diet-induced exercise intolerance and metabolic inflexibility. PLoS One 2015; 10(8): e13492-134.
[http://dx.doi.org/10.1371/journal.pone.0134927] [PMID: 26287487]
[57]
Zhang J, Wei C, Wang H, Tang S, Jia Z, Wang L, et al. Protective effect of qiliqiangxin capsule on energy metabolism and myocardial mitochondria in pressure overload heart failure rats. Evid Based Complement Alternat Med 2013; 2013: 378298.
[http://dx.doi.org/10.1155/2013/378298]

Rights & Permissions Print Cite
Article Metrics
86
6
© 2024 Bentham Science Publishers | Privacy Policy