The Role of Bioactive Small Molecules in COPD Pathogenesis

References

• Wang C, Xu J, Yang L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China pulmonary health [CPH] study): a national cross-sectional study. Lancet. 2018;391(10131):1–10. doi:10.1016/S0140-6736(18)30841-9.
   PubMed Web of Science ®Google Scholar
• Venkatesan P. Gold copd report: 2023 update. Lancet Respir Med. 2023;11(1):18. doi:10.1016/S2213-2600(22)00494-5.
   PubMed Web of Science ®Google Scholar
• Fang L, Gao P, Bao H, et al. Chronic obstructive pulmonary disease in China: a nationwide prevalence study. Lancet Respir Med. 2018;6(6):421–430. doi:10.1016/S2213-2600(18)30103-6.
   PubMed Web of Science ®Google Scholar
• Nucera F, Hansbro PM, Paudel KR, et al. Chapter 14 - Role of autoimmunity in the pathogenesis of chronic obstructive pulmonary disease and pulmonary emphysema. In: Nima Rezaei, editor, Translational autoimmunity, volume 3 of translational immunology. London: Academic Press, 2022. p. 311–331. doi:10.1016/B978-0-323-85415-3.00003-9.
   Google Scholar
• Nucera F, Mumby S, Paudel KR, et al. Role of oxidative stress in the pathogenesis of COPD. Minerva Med. 2022;113(3):370–404. doi:10.23736/S0026-4806.22.07972-1.
   PubMed Web of Science ®Google Scholar
• Cioni G, Marcucci R, Gori AM, et al. Increased homocysteine and lipoprotein(a) levels highlight systemic atherosclerotic burden in patients with a history of acute coronary syndromes. J Vasc Surg. 2016;64(1):163–170. doi:10.1016/j.jvs.2016.01.056.
   PubMed Web of Science ®Google Scholar
• Andersson A, Ankerst J, Lindgren A, et al. Hyperhomocysteinemia and changed plasma thiol redox status in chronic obstructive pulmonary disease. Clin Chem Lab Med. 2001;39(3):229–233. Mar
   PubMed Web of Science ®Google Scholar
• Chaudhary D, Sharma N, Senapati S. Serum homocysteine could be used as a predictive marker for chronic obstructive pulmonary disease: a meta-analysis. Front Public Health. 2019;7:69. doi:10.3389/fpubh.2019.00069.
   PubMed Web of Science ®Google Scholar
• Täger M, Piecyk A, Hnlein T, et al. Evidence of a defective thiol status of alveolar macrophages from COPD patients and smokers. Chronic obstructive pulmonary disease. Free Radic Biol Med. 2000;29(11):1160–1165. doi:10.1016/s0891-5849(00)00424-x.
   PubMedGoogle Scholar
• Mujumdar VS, Tummalapalli CM, Aru GM, et al. Mechanism of constrictive vascular remodeling by homocysteine: role of PPAR. Am J Physiol Cell Physiol. 2002;282(5):C1009–1015. doi:10.1152/ajpcell.00353.2001.
   PubMed Web of Science ®Google Scholar
• Rodrigo R, Passalacqua W, Araya J, et al. Implications of oxidative stress and homocysteine in the pathophysiology of essential hypertension. J Cardiovasc Pharmacol. 2003;42(4):453–461. doi:10.1097/00005344-200310000-00001.
   PubMed Web of Science ®Google Scholar
• Zhang L, Jin M, Hu XS, et al. Homocysteine stimulates nuclear factor kappaB activity and interleukin-6 expression in rat vascular smooth muscle cells. Cell Biol Int. 2006;30(7):592–597. doi:10.1016/j.cellbi.2006.03.007.
   PubMed Web of Science ®Google Scholar
• Ji J, Feng M, Niu X, et al. Liraglutide blocks the proliferation, migration and phenotypic switching of homocysteine (hcy)-induced vascular smooth muscle cells (VSMCs) by suppressing proprotein convertase subtilisin kexin9 (PCSK9)/ low-density lipoprotein receptor (LDLR). Bioengineered. 2021;12(1):8057–8066. Dec doi: 10.1080/21655979.2021.1982304.
   PubMed Web of Science ®Google Scholar
• Chambers JC, McGregor A, Jean-Marie J, et al. Acute hyperhomocysteinaemia and endothelial dysfunction. Lancet. 1998;351(9095):36–37. doi:10.1016/S0140-6736(05)78090-9.
   PubMed Web of Science ®Google Scholar
• Okatani Y, Wakatsuki A, Reiter RJ. Protective effect of melatonin against homocysteine-induced vasoconstriction of human umbilical artery. Biochem Biophys Res Commun. 2000;277(2):470–475. doi:10.1006/bbrc.2000.3687.
   PubMed Web of Science ®Google Scholar
• Zhang X, Wang X, Zhang J, et al. Effects of taurine on alterations of neurobehavior and neurodevelopment key proteins expression in infant rats by exposure to hexabromocyclododecane. Adv Exp Med Biol. 2017;975(Pt 1):119–130.
   PubMedGoogle Scholar
• Jong CJ, Azuma J, Schaffer S. Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids. 2012;42(6):2223–2232. doi:10.1007/s00726-011-0962-7.
   PubMed Web of Science ®Google Scholar
• Li X, Yang H, Sun H, et al. Taurine ameliorates particulate matter-induced emphysema by switching on mitochondrial NADH dehydrogenase genes. Proc Natl Acad Sci U S A. 2017;114(45):E9655–E9664.
   PubMed Web of Science ®Google Scholar
• Thalacker-Mercer AE, Gheller ME. Benefits and adverse effects of histidine supplementation. J Nutr. 2020;150(Suppl 1):2588S–2592S. doi:10.1093/jn/nxaa229.
   PubMedGoogle Scholar
• Diao W, Labaki WW, Han MK, et al. Disruption of histidine and energy homeostasis in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2019;14:2015–2025. doi:10.2147/COPD.S210598.
   PubMed Web of Science ®Google Scholar
• Ghosh N, Choudhury P, Subramani E, et al. Metabolomic signatures of asthma-COPD overlap (ACO) are different from asthma and COPD. Metabolomics. 2019;15(6):87. doi:10.1007/s11306-019-1552-z.
   PubMed Web of Science ®Google Scholar
• Peng L, You H, Xu MY, et al. A novel metabolic score for predicting the acute exacerbation in patients with chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2023;18:785–795. doi:10.2147/COPD.S405547.
   PubMed Web of Science ®Google Scholar
• Tian Q, Xu M, He B. Histidine ameliorates elastase- and lipopolysaccharide-induced lung inflammation by inhibiting the activation of the NLRP3 inflammasome. Acta Biochim Biophys Sin (Shanghai). 2021;53(8):1055–1064. doi:10.1093/abbs/gmab072.
   PubMed Web of Science ®Google Scholar
• Us P, Cotgreave IA, Berggren M. Lung protection by a thiol-containing antioxidant: n -acetylcysteine. Respiration. 1986;50(Suppl 1):31–42.
   Google Scholar
• Bridgeman MM, Marsden M, MacNee W, et al. Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine. Thorax. 1991;46(1):39–42. doi:10.1136/thx.46.1.39.
   PubMed Web of Science ®Google Scholar
• Rtensson J, Jain A, Frayer W, et al. Glutathione metabolism in the lung: inhibition of its synthesis leads to lamellar body and mitochondrial defects. Proc Natl Acad Sci U S A. 1989;86(14):5296–5300. doi:10.1073/pnas.86.14.5296.
   PubMed Web of Science ®Google Scholar
• Simon LM, Suttorp N. Lung cell oxidant injury: decrease in oxidant mediated cytotoxicity by N-acetylcysteine. Eur J Respir Dis Suppl. 1985;139:132–135.
   PubMedGoogle Scholar
• Conklin DJ, Haberzettl P, Prough RA, et al. Glutathione-S-transferase P protects against endothelial dysfunction induced by exposure to tobacco smoke. Am J Physiol Heart Circ Physiol. 2009;296(5):H1586–1597. doi:10.1152/ajpheart.00867.2008.
   PubMed Web of Science ®Google Scholar
• Cotgreave IA. N-acetylcysteine: pharmacological considerations and experimental and clinical applications. Adv Pharmacol. 1997;38:205–227.
   PubMedGoogle Scholar
• Dekhuijzen PN. Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease. Eur Respir J. 2004;23(4):629–636. doi:10.1183/09031936.04.00016804.
   PubMed Web of Science ®Google Scholar
• Sadowska AM, Manuel-Y-Keenoy B, De Backer WA. Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulm Pharmacol Ther. 2007;20(1):9–22. doi:10.1016/j.pupt.2005.12.007.
   PubMed Web of Science ®Google Scholar
• Santangelo F. Intracellular thiol concentration modulating inflammatory response: influence on the regulation of cell functions through cysteine prodrug approach. Curr Med Chem. 2003;10(23):2599–2610. doi:10.2174/0929867033456567.
   PubMed Web of Science ®Google Scholar
• Grinberg L, Fibach E, Amer J, et al. N-acetylcysteine amide, a novel cell-permeating thiol, restores cellular glutathione and protects human red blood cells from oxidative stress. Free Radic Biol Med. 2005;38(1):136–145. doi:10.1016/j.freeradbiomed.2004.09.025.
   PubMed Web of Science ®Google Scholar
• Rahman I, MacNee W. Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radic Biol Med. 2000;28(9):1405–1420. doi:10.1016/s0891-5849(00)00215-x.
   PubMed Web of Science ®Google Scholar
• Mazor D, Golan E, Philip V, et al. Red blood cell permeability to thiol compounds following oxidative stress. Eur J Haematol. 1996;57(3):241–246. doi:10.1111/j.1600-0609.1996.tb01370.x.
   PubMed Web of Science ®Google Scholar
• Reddy NM, Kleeberger SR, Bream JH, et al. Genetic disruption of the Nrf2 compromises cell-cycle progression by impairing GSH-induced redox signaling. Oncogene. 2008;27(44):5821–5832. doi:10.1038/onc.2008.188.
   PubMed Web of Science ®Google Scholar
• Dekhuijzen PN, van Beurden WJ. The role for N-acetylcysteine in the management of COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(2):99–106. doi:10.2147/copd.2006.1.2.99.
   PubMedGoogle Scholar
• De Benedetto F, Aceto A, Dragani B, et al. Long-term oral n-acetylcysteine reduces exhaled hydrogen peroxide in stable COPD. Pulm Pharmacol Ther. 2005;18(1):41–47. doi:10.1016/j.pupt.2004.09.030.
   PubMed Web of Science ®Google Scholar
• Stey C, Steurer J, Bachmann S, et al. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J. 2000;16(2):253–262. doi:10.1034/j.1399-3003.2000.16b12.x.
   PubMed Web of Science ®Google Scholar
• Koechlin C, Couillard A, Cristol JP, et al. Does systemic inflammation trigger local exercise-induced oxidative stress in COPD? Eur Respir J. 2004;23(4):538–544. doi:10.1183/09031936.04.00069004.
   PubMed Web of Science ®Google Scholar
• Decramer M, Lken M, Dekhuijzen PN, et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (bronchitis randomized on NAC Cost-Utility study, BRONCUS): a randomised placebo-controlled trial. Lancet. 2005;365(9470):1552–1560. doi:10.1016/S0140-6736(05)66456-2.
   PubMed Web of Science ®Google Scholar
• Schaffer SW, Azuma J, Mozaffari M. Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol. 2009;87(2):91–99. doi:10.1139/Y08-110.
   PubMed Web of Science ®Google Scholar
• Campbell JD, McDonough JE, Zeskind JE, et al. A gene expression signature of emphysema-related lung destruction and its reversal by the tripeptide GHK. Genome Med. 2012;4(8):67. doi:10.1186/gm368.
   PubMedGoogle Scholar
• Hur GH, Han SC, Ryu AR, et al. Effect of oligoarginine conjugation on the antiwrinkle activity and transdermal delivery of GHK peptide. J Pept Sci. 2020;26(2):e3234.
   PubMed Web of Science ®Google Scholar
• Boo S, Dagnino L. Integrins as modulators of transforming growth factor beta signaling in dermal fibroblasts during skin regeneration after injury. Adv Wound Care (New Rochelle). 2013;2(5):238–246. doi:10.1089/wound.2012.0394.
   PubMedGoogle Scholar
• Ma WH, Li M, Ma HF, et al. Protective effects of GHK-Cu in bleomycin-induced pulmonary fibrosis via anti-oxidative stress and anti-inflammation pathways. Life Sci. 2020;241:117139. doi:10.1016/j.lfs.2019.117139.
   PubMed Web of Science ®Google Scholar
• Park JR, Lee H, Kim SI, et al. The tri-peptide GHK-Cu complex ameliorates lipopolysaccharide-induced acute lung injury in mice. Oncotarget. 2016;7(36):58405–58417. doi:10.18632/oncotarget.11168.
   PubMedGoogle Scholar
• Bell D, McDermott BJ. Calcitonin gene-related peptide in the cardiovascular system: characterization of receptor populations and their (patho)physiological significance. Pharmacol Rev. 1996;48(2):253–288.
   PubMed Web of Science ®Google Scholar
• Dakhama A, Larsen GL, Gelfand EW. Calcitonin gene-related peptide: role in airway homeostasis. Curr Opin Pharmacol. 2004;4(3):215–220. doi:10.1016/j.coph.2004.01.006.
   PubMed Web of Science ®Google Scholar
• Cadieux A, Springall DR, Mulderry PK, et al. Occurrence, distribution and ontogeny of CGRP immunoreactivity in the rat lower respiratory tract: effect of capsaicin treatment and surgical denervations. Neuroscience. 1986;19(2):605–627. doi:10.1016/0306-4522(86)90285-x.
   PubMed Web of Science ®Google Scholar
• Lundberg JM, Franco-Cereceda A, Hua X, et al. Co-existence of substance P and calcitonin gene-related peptide-like immunoreactivities in sensory nerves in relation to cardiovascular and bronchoconstrictor effects of capsaicin. Eur J Pharmacol. 1985;108(3):315–319. doi:10.1016/0014-2999(85)90456-x.
   PubMed Web of Science ®Google Scholar
• Keith IM, Pelto-Huikko M, Schalling M, et al. Calcitonin gene-related peptide and its mRNA in pulmonary neuroendocrine cells and ganglia. Histochemistry. 1991;96(4):311–315. doi:10.1007/BF00271351.
   PubMedGoogle Scholar
• Reynolds SD, Giangreco A, Power JH, et al. Neuroepithelial bodies of pulmonary airways serve as a reservoir of progenitor cells capable of epithelial regeneration. Am J Pathol. 2000;156(1):269–278. doi:10.1016/S0002-9440(10)64727-X.
   PubMed Web of Science ®Google Scholar
• Keith IM. The role of endogenous lung neuropeptides in regulation of the pulmonary circulation. Physiol Res. 2000;49(5):519–537.
   PubMed Web of Science ®Google Scholar
• A, Dakhama A, Kanehiro MJä, JE, Loader, et al. Regulation of airway hyperresponsiveness by calcitonin gene-related peptide in allergen sensitized and challenged mice. Am J Respir Crit Care Med. 2002;165(8):1137–1144. doi:10.1164/ajrccm.165.8.2109058.
   PubMed Web of Science ®Google Scholar
• Li WJ, Wang TK. Calcitonin gene-related peptide inhibits interleukin-1beta-induced interleukin-8 secretion in human type II alveolar epithelial cells. Acta Pharmacol Sin. 2006;27(10):1340–1345. doi:10.1111/j.1745-7254.2006.00408.x.
   PubMed Web of Science ®Google Scholar
• Li W, Wang T, Ma C, et al. Calcitonin gene-related peptide inhibits interleukin-1beta-induced endogenous monocyte chemoattractant protein-1 secretion in type II alveolar epithelial cells. Am J Physiol Cell Physiol. 2006;291(3):C456–465. doi:10.1152/ajpcell.00538.2005.
   PubMed Web of Science ®Google Scholar
• Olopade CO, Yu J, Abubaker J, et al. Catalytic hydrolysis of VIP in pregnant women with asthma. J Asthma. 2006;43(6):429–432. doi:10.1080/02770900600710730.
   PubMed Web of Science ®Google Scholar
• Kajimura M, Fukuda R, Bateman RM, et al. Interactions of multiple gas-transducing systems: hallmarks and uncertainties of CO, NO, and H2S gas biology. Antioxid Redox Signal. 2010;13(2):157–192. doi:10.1089/ars.2009.2657.
   PubMed Web of Science ®Google Scholar
• Ryter SW, Choi AM. Carbon monoxide in exhaled breath testing and therapeutics. J Breath Res. 2013;7(1):017111. doi:10.1088/1752-7155/7/1/017111.
   PubMed Web of Science ®Google Scholar
• SW, Ryter K, C, Ma, AMK, Choi. Carbon monoxide in lung cell physiology and disease. Am J Physiol Cell Physiol. 2018;314(2):C211–C227. doi:10.1152/ajpcell.00022.2017.
   PubMed Web of Science ®Google Scholar
• Dong SA, Zhang Y, Yu JB, et al. Carbon monoxide attenuates lipopolysaccharide-induced lung injury by mitofusin proteins via p38 MAPK pathway. J Surg Res. 2018;228:201–210. doi:10.1016/j.jss.2018.03.042.
   PubMed Web of Science ®Google Scholar
• Hendriks KD, Maassen H, van Dijk PR, et al. Gasotransmitters in health and disease: a mitochondria-centered view. Curr Opin Pharmacol. 2019;45:87–93. doi:10.1016/j.coph.2019.07.001.
   PubMed Web of Science ®Google Scholar
• Otterbein LE, Bach FH, Alam J, et al. Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med. 2000;6(4):422–428. doi:10.1038/74680.
   PubMed Web of Science ®Google Scholar
• Chen FJ, Huang XY, Liu YL, et al. Importance of fractional exhaled nitric oxide in the differentiation of asthma-COPD overlap syndrome, asthma, and COPD. Int J Chron Obstruct Pulmon Dis. 2016;11:2385–2390. doi:10.2147/COPD.S115378.
   PubMed Web of Science ®Google Scholar
• Liao CC, Chen YH, Lin F, et al. Hydrogen sulfide inhibits transforming growth factor beta-1 induced bronchial epithelial-mesenchymal transition. Chin Med J (Engl). 2015;128(23):3247–3250. doi:10.4103/0366-6999.170266.
   PubMed Web of Science ®Google Scholar
• Wang Y, Liao S, Pan Z, et al. Hydrogen sulfide alleviates particulate matter-induced emphysema and airway inflammation by suppressing ferroptosis. Free Radic Biol Med. 2022;186:1–16. doi:10.1016/j.freeradbiomed.2022.04.014.
   PubMed Web of Science ®Google Scholar
• Wang L, Meng J, Wang C, et al. 1/Smad pathway. Exp Biol Med (Maywood). 2020;245(3):190–200. doi:10.1177/1535370220904342.
   PubMed Web of Science ®Google Scholar
• Xu C, Wang L, Fozouni P, et al. SIRT1 is downregulated by autophagy in senescence and ageing. Nat Cell Biol. 2020;22(10):1170–1179. doi:10.1038/s41556-020-00579-5.
   PubMed Web of Science ®Google Scholar
• Guan R, Cai Z, Wang J, et al. Hydrogen sulfide attenuates mitochondrial dysfunction-induced cellular senescence and apoptosis in alveolar epithelial cells by upregulating sirtuin 1. Aging (Albany NY). 2019;11(24):11844–11864. doi:10.18632/aging.102454.
   PubMedGoogle Scholar
• Lin F, Liao C, Zhang J, et al. Hydrogen sulfide inhibits bronchial epithelial cell epithelial mesenchymal transition through regulating endoplasm reticulum stress. Front Mol Biosci. 2022;9:828766. doi:10.3389/fmolb.2022.828766.
   PubMed Web of Science ®Google Scholar
• Ding HB, Liu KX, Huang JF, et al. Protective effect of exogenous hydrogen sulfide on pulmonary artery endothelial cells by suppressing endoplasmic reticulum stress in a rat model of chronic obstructive pulmonary disease. Biomed Pharmacother. 2018;105:734–741. doi:10.1016/j.biopha.2018.05.131.
   PubMed Web of Science ®Google Scholar
• Guan R, Wang J, Li D, et al. /MAPK signaling pathway. Int Immunopharmacol. 2020;81:105979. doi:10.1016/j.intimp.2019.105979.
   PubMed Web of Science ®Google Scholar
• Wang L, Meng J, Wang C, et al. B signaling pathway. Int J Mol Med. 2022b;49(5):1–13. doi: 10.3892/ijmm.2022.5112.
   PubMedGoogle Scholar
• Pacitti D, Scotton CJ, Kumar V, et al. Gasping for sulfide: a critical appraisal of hydrogen sulfide in lung disease and accelerated aging. Antioxid Redox Signal. 2021;35(7):551–579. doi:10.1089/ars.2021.0039.
   PubMed Web of Science ®Google Scholar
• Sun Y, Wang K, Li MX, et al. Metabolic changes of H2S in smokers and patients of COPD which might involve in inflammation, oxidative stress and steroid sensitivity. Sci Rep. 2015;5(1):14971. doi:10.1038/srep14971.
   PubMedGoogle Scholar
• Fritscher LG, Post M, Rodrigues MT, et al. Profile of eicosanoids in breath condensate in asthma and COPD. J Breath Res. 2012;6(2):026001. doi:10.1088/1752-7155/6/2/026001.
   PubMed Web of Science ®Google Scholar
• Goldkorn T, Ravid T, Khan EM. Life and death decisions: ceramide generation and EGF receptor trafficking are modulated by oxidative stress. Antioxid Redox Signal. 2005;7(1–2):119–128. doi:10.1089/ars.2005.7.119.
   PubMed Web of Science ®Google Scholar
• Agudelo CW, Kumley BK, Area-Gomez E, et al. Decreased surfactant lipids correlate with lung function in chronic obstructive pulmonary disease (COPD). PLoS One. 2020;15(2):e0228279. doi:10.1371/journal.pone.0228279.
   PubMed Web of Science ®Google Scholar
• Rutting S, Zakarya R, Bozier J, et al. Dietary fatty acids amplify inflammatory responses to infection through p38 MAPK signaling. Am J Respir Cell Mol Biol. 2019;60(5):554–568. doi:10.1165/rcmb.2018-0215OC.
   PubMed Web of Science ®Google Scholar
• Rutting S, Papanicolaou M, Xenaki D, et al. 6 Polyunsaturated fatty acid arachidonic acid increases inflammation, but inhibits ECM protein expression in COPD. Respir Res. 2018;19(1):211. doi:10.1186/s12931-018-0919-4.
   PubMedGoogle Scholar
• Agudelo CW, Samaha G, Garcia-Arcos I. Alveolar lipids in pulmonary disease. A review. Lipids Health Dis. 2020;19(1):122. doi:10.1186/s12944-020-01278-8.
   PubMed Web of Science ®Google Scholar
• Tibboel J, Reiss I, de Jongste JC, et al. Ceramides: a potential therapeutic target in pulmonary emphysema. Respir Res. 2013;14(1):96. doi:10.1186/1465-9921-14-96.
   PubMedGoogle Scholar
• Zhang Y, Yao B, Delikat S, et al. Kinase suppressor of ras is ceramide-activated protein kinase. Cell. 1997;89(1):63–72. doi:10.1016/s0092-8674(00)80183-x.
   PubMed Web of Science ®Google Scholar
• Chalfant CE, Rathman K, Pinkerman RL, et al. De novo ceramide regulates the alternative splicing of caspase 9 and bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1. J Biol Chem. 2002;277(15):12587–12595. doi:10.1074/jbc.M112010200.
   PubMed Web of Science ®Google Scholar
• Heinrich M, Wickel M, Winoto-Morbach S, et al. Ceramide as an activator lipid of cathepsin D. Adv Exp Med Biol. 2000;477:305–315. doi:10.1007/0-306-46826-3_33.
   PubMed Web of Science ®Google Scholar
• Giordano RJ, Lahdenranta J, Zhen L, et al. Targeted induction of lung endothelial cell apoptosis causes emphysema-like changes in the mouse. J Biol Chem. 2008;283(43):29447–29460. doi:10.1074/jbc.M804595200.
   PubMed Web of Science ®Google Scholar
• Petrache I, Natarajan V, Zhen L, et al. Ceramide upregulation causes pulmonary cell apoptosis and emphysema-like disease in mice. Nat Med. 2005;11(5):491–498. doi:10.1038/nm1238.
   PubMed Web of Science ®Google Scholar
• Huang YL, Sheu JY, Lin TH. Association between oxidative stress and changes of trace elements in patients with breast cancer. Clin Biochem. 1999;32(2):131–136. doi:10.1016/s0009-9120(98)00096-4.
   PubMed Web of Science ®Google Scholar
• Read SA, Obeid S, Ahlenstiel C, et al. The role of zinc in antiviral immunity. Adv Nutr. 2019;10(4):696–710. doi:10.1093/advances/nmz013.
   PubMed Web of Science ®Google Scholar
• Wang M, Phadke M, Packard D, et al. Zinc: roles in pancreatic physiology and disease. Pancreatology. 2020;20(7):1413–1420. doi:10.1016/j.pan.2020.08.016.
   PubMed Web of Science ®Google Scholar
• Skalny AV, Aschner M, Tinkov AA. Zinc. Adv Food Nutr Res. 2021;96:251–310.
   PubMedGoogle Scholar
• Roscioli E, Tran HB, Jersmann H, et al. The uncoupling of autophagy and zinc homeostasis in airway epithelial cells as a fundamental contributor to COPD. Am J Physiol Lung Cell Mol Physiol. 2017;313(3):L453–L465. doi:10.1152/ajplung.00083.2017.
   PubMed Web of Science ®Google Scholar
• Lin YS, Caffrey JL, Chang MH, et al. Cigarette smoking, cadmium exposure, and zinc intake on obstructive lung disorder. Respir Res. 2010;11(1):53. doi:10.1186/1465-9921-11-53.
   PubMedGoogle Scholar
• Raguso CA, Luthy C. Nutritional status in chronic obstructive pulmonary disease: role of hypoxia. Nutrition. 2011;27(2):138–143. doi:10.1016/j.nut.2010.07.009.
   PubMed Web of Science ®Google Scholar
• Herzog R, Cunningham-Rundles S. Immunologic impact of nutrient depletion in chronic obstructive pulmonary disease. Curr Drug Targets. 2011;12(4):489–500. doi:10.2174/138945011794751500.
   PubMed Web of Science ®Google Scholar
• Karadag F, Cildag O, Altinisik M, et al. Trace elements as a component of oxidative stress in COPD. Respirology. 2004;9(1):33–37. doi:10.1111/j.1440-1843.2003.00534.x.
   PubMed Web of Science ®Google Scholar
• El-Attar M, Said M, El-Assal G, et al. Serum trace element levels in COPD patient: the relation between trace element supplementation and period of mechanical ventilation in a randomized controlled trial. Respirology. 2009;14(8):1180–1187. doi:10.1111/j.1440-1843.2009.01622.x.
   PubMed Web of Science ®Google Scholar
• Anetor JI, Ajose F, Anetor GO, et al. High cadmium / zinc ratio in cigarette smokers: potential implications as a biomarker of risk of prostate cancer. Niger J Physiol Sci. 2008;23(1–2):41–49.
   PubMedGoogle Scholar
• Kazi TG, Wadhwa SK, Afridi HI, et al. Evaluation of cadmium and zinc in biological samples of tobacco and alcohol user male mouth cancer patients. Hum Exp Toxicol. 2010;29(3):221–230. doi:10.1177/0960327109360045.
   PubMed Web of Science ®Google Scholar
• Kırkıl G, Hamdi Muz M, Seçkin D, et al. Antioxidant effect of zinc picolinate in patients with chronic obstructive pulmonary disease. Respir Med. 2008;102(6):840–844. doi:10.1016/j.rmed.2008.01.010.
   PubMed Web of Science ®Google Scholar
• MacDonald RS. The role of zinc in growth and cell proliferation. J Nutr. 2000;130(5S Suppl):1500S–1508S. doi:10.1093/jn/130.5.1500S.
   PubMedGoogle Scholar
• Liu X, Ali MK, Dua K, et al. The role of zinc in the pathogenesis of lung disease. Nutrients. 2022;14(10):1–14. doi:10.3390/nu14102115.
   Web of Science ®Google Scholar
• Gogoi K, Manna P, Dey T, et al. Circulatory heavy metals (cadmium, lead, mercury, and chromium) inversely correlate with plasma GST activity and GSH level in COPD patients and impair NOX4/Nrf2/GCLC/GST signaling pathway in cultured monocytes. Toxicol in Vitro. 2019;54:269–279. doi:10.1016/j.tiv.2018.10.010.
   PubMed Web of Science ®Google Scholar
• Weichenthal S, Shekarrizfard M, Kulka R, et al. Spatial variations in the estimated production of reactive oxygen species in the epithelial lung lining fluid by iron and copper in fine particulate air pollution. Environ Epidemiol. 2018;2(3):e020. doi:10.1097/EE9.0000000000000020.
   PubMedGoogle Scholar
• Qi W, Liu L, Zeng Q, et al. Contribution of cuproptosis and Cu metabolism-associated genes to chronic obstructive pulmonary disease. J Cell Mol Med. 2023;27(24):4034–4044. doi:10.1111/jcmm.17985.
   PubMed Web of Science ®Google Scholar