{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T06:43:49Z","timestamp":1791269029360,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2017,6,10]],"date-time":"2017-06-10T00:00:00Z","timestamp":1497052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2016R1A2B4013627"],"award-info":[{"award-number":["2016R1A2B4013627"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Insulin resistance (IR) is an important stress factor in the central nervous system, thereby aggravating neuropathogenesis and triggering cognitive decline. Melatonin, which is an antioxidant phytochemical and synthesized by the pineal gland, has multiple functions in cellular responses such as apoptosis and survival against stress. This study investigated whether melatonin modulates the signaling of neuronal cell death induced by endoplasmic reticulum (ER) stress under IR condition using SH-SY5Y neuroblastoma cells. Apoptosis cell death signaling markers (cleaved Poly [ADP-ribose] polymerase 1 (PARP), p53, and Bax) and ER stress markers (phosphorylated eIF2\u03b1 (p-eIF2\u03b1), ATF4, CHOP, p-IRE1, and spliced XBP1 (sXBP1)) were measured using reverse transcription-PCR, quantitative PCR, and western blottings. Immunofluorescence staining was also performed for p-ASK1 and p-IRE1. The mRNA or protein expressions of cell death signaling markers and ER stress markers were increased under IR condition, but significantly attenuated by melatonin treatment. Insulin-induced activation of ASK1 (p-ASK1) was also dose dependently attenuated by melatonin treatment. The regulatory effect of melatonin on neuronal cells under IR condition was associated with ASK1 signaling. In conclusion, the result suggested that melatonin may alleviate ER stress under IR condition, thereby regulating neuronal cell death signaling.<\/jats:p>","DOI":"10.3390\/nu9060593","type":"journal-article","created":{"date-parts":[[2017,6,12]],"date-time":"2017-06-12T10:27:59Z","timestamp":1497263279000},"page":"593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Melatonin Modulates Neuronal Cell Death Induced by Endoplasmic Reticulum Stress under Insulin Resistance Condition"],"prefix":"10.3390","volume":"9","author":[{"given":"Juhyun","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, Center for Creative Biomedical Scientists at Chonnam National University, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9262-3309","authenticated-orcid":false,"given":"Oh","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Food Sciences and Nutrition, Dong-A University, 37 550beon-gil Nakdongdaero, Saha-gu, Busan 49315, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/S0140-6736(13)62154-6","article-title":"Pathophysiology and treatment of type 2 diabetes: Perspectives on the past, present, and future","volume":"383","author":"Kahn","year":"2014","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/S1474-4422(14)70249-2","article-title":"Cognitive function in patients with diabetes mellitus: Guidance for daily care","volume":"14","author":"Koekkoek","year":"2015","journal-title":"Lancet Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/jdi.12087","article-title":"Diabetes mellitus and risk of dementia: A meta-analysis of prospective observational studies","volume":"4","author":"Gudala","year":"2013","journal-title":"J. Diabetes Investig."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/S2213-8587(13)70088-3","article-title":"Dementia and cognitive decline in type 2 diabetes and prediabetic stages: Towards targeted interventions","volume":"2","author":"Biessels","year":"2014","journal-title":"Lancet Diabetes Edocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1073\/pnas.0336073100","article-title":"Reduced glucose tolerance is associated with poor memory performance and hippocampal atrophy among normal elderly","volume":"100","author":"Convit","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1080\/13803390903224928","article-title":"Cognitive impairment in nondiabetic middle-aged and older adults is associated with insulin resistance","volume":"32","author":"Bruehl","year":"2010","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1037\/0735-7044.110.3.451","article-title":"Cognitive impairment in rats fed high-fat diets: A specific effect of saturated fatty-acid intake","volume":"110","author":"Greenwood","year":"1996","journal-title":"Behav. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7036","DOI":"10.1073\/pnas.1000645107","article-title":"Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes","volume":"107","author":"Takeda","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1074\/jbc.R113.534743","article-title":"Unfolded protein response signaling and metabolic diseases","volume":"289","author":"Lee","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.ceca.2014.08.006","article-title":"Endoplasmic reticulum stress in insulin resistance and diabetes","volume":"56","author":"DeJesus","year":"2014","journal-title":"Cell Calcium"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1038\/sj.cdd.4401373","article-title":"Roles of CHOP\/GADD153 in endoplasmic reticulum stress","volume":"11","author":"Oyadomari","year":"2004","journal-title":"Cell Death Differ."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/sj.embor.7400779","article-title":"Mediators of endoplasmic reticulum stress-induced Apoptosis","volume":"7","author":"Szegezdi","year":"2006","journal-title":"EMBO Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1126\/science.1101902","article-title":"A selective inhibitor of eIF2\u03b1 dephosphorylation protects cells from ER stress","volume":"307","author":"Boyce","year":"2005","journal-title":"Science"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/sj.emboj.7600596","article-title":"TRB3, a novel ER stress-ind, ucible gene, is induced via ATF4\u2013CHOP pathway and is involved in cell death","volume":"24","author":"Ohoka","year":"2005","journal-title":"EMBO J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3066","DOI":"10.1101\/gad.1250704","article-title":"CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum","volume":"18","author":"Marciniak","year":"2004","journal-title":"Gene Dev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s00125-011-2427-7","article-title":"Deletion of C\/EBP homologous protein (Chop) in C57Bl\/6 mice dissociates obesity from insulin resistance","volume":"55","author":"Maris","year":"2012","journal-title":"Diabetologia"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.canlet.2012.04.009","article-title":"The BH3 mimetic S1 induces autophagy through ER stress and disruption of Bcl-2\/Beclin 1 interaction in human glioma U251 cells","volume":"323","author":"Zhong","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.2353\/ajpath.2009.080864","article-title":"Positive role of CCAAT\/enhancer-binding protein homologous protein, a transcription factor involved in the endoplasmic reticulum stress response in the development of colitis","volume":"174","author":"Namba","year":"2009","journal-title":"Am. J. Pathol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0092-8674(01)00611-0","article-title":"XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor","volume":"107","author":"Yoshida","year":"2001","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5708","DOI":"10.1093\/emboj\/17.19.5708","article-title":"Cloning of mammalian Ire1 reveals diversity in the ER stress responses","volume":"17","author":"Wang","year":"1998","journal-title":"EMBO J."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7448","DOI":"10.1128\/MCB.23.21.7448-7459.2003","article-title":"XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response","volume":"23","author":"Lee","year":"2003","journal-title":"Mol. Cell. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.2337\/db08-0604","article-title":"Increase in endoplasmic reticulum stress-related proteins and genes in adipose tissue of obese, insulin-resistant individuals","volume":"57","author":"Boden","year":"2008","journal-title":"Diabetes"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.bbrc.2007.11.182","article-title":"Direct monitoring of in vivo ER stress during the development of insulin resistance with ER stress-activated indicator transgenic mice","volume":"366","author":"Yoshiuchi","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/S1097-2765(00)80283-X","article-title":"ASK1 is essential for JNK\/SAPK activation by TRAF2","volume":"2","author":"Nishitoh","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1126\/science.275.5296.90","article-title":"Induction of apoptosis by ASK1, a mammalian MAPKKK that activates SAPK\/JNK and p38 signaling pathways","volume":"275","author":"Ichijo","year":"1997","journal-title":"Science"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1146\/annurev.pharmtox.48.113006.094606","article-title":"Apoptosis signal-regulating kinase 1 in stress and immune response","volume":"48","author":"Takeda","year":"2008","journal-title":"Annu. Rev. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1128\/MCB.20.1.196-204.2000","article-title":"Role of apoptosis signal-regulating kinase in regulation of the c-Jun N-terminal kinase pathway and apoptosis in sympathetic neurons","volume":"20","author":"Kanamoto","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"26576","DOI":"10.1074\/jbc.M003412200","article-title":"Execution of apoptosis signal-regulating kinase 1 (ASK1)-induced apoptosis by the mitochondria-dependent caspase activation","volume":"275","author":"Hatai","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1517\/14728222.2013.756471","article-title":"Targeting endoplasmic reticulum stress in metabolic disease","volume":"17","author":"Cao","year":"2013","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"801","DOI":"10.4161\/auto.23961","article-title":"TECPR2: A new autophagy link for neurodegeneration","volume":"9","author":"Gelman","year":"2013","journal-title":"Autophagy"},{"key":"ref_31","first-page":"635172","article-title":"Melatonin modulates endoplasmic reticulum stress and Akt\/GSK3-beta signaling pathway in a rat model of renal warm ischemia reperfusion","volume":"2015","author":"Zaouali","year":"2015","journal-title":"Anal. Cell. Pathol. (Amst.)"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Meng, X., Li, Y., Li, S., Zhou, Y., Gan, R.Y., Xu, D.P., and Li, H.B. (2017). Dietary Sources and Bioactivities of Melatonin. Nutrients, 9.","DOI":"10.3390\/nu9040367"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1111\/j.1742-1241.2006.01191.x","article-title":"Melatonin: Therapeutic and clinical utilization","volume":"61","author":"Altun","year":"2007","journal-title":"Int. J. Clin. Pract."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1016\/j.foodchem.2006.12.010","article-title":"Melatonin is a phytochemical in olive oil","volume":"104","author":"Lardone","year":"2007","journal-title":"Food Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1111\/jpi.12264","article-title":"Melatonin and endoplasmic reticulum stress: Relation to autophagy and apoptosis","volume":"59","author":"Fernandez","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-079X.2012.01014.x","article-title":"A review ofthe molecular aspects of melatonin\u2019s anti-inflammatory actions: Recent insights and new perspectives","volume":"54","author":"Mauriz","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/j.1600-079X.2010.00807.x","article-title":"Melatonin attenuates apoptotic liver damage in fulminant hepatic failure induced by the rabbit hemorrhagic disease virus","volume":"50","author":"Tunon","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/j.1600-079X.2007.00504.x","article-title":"Cytoprotective effects of melatonin against necrosis and apoptosis induced by ischemia\/reperfusion injury in rat liver","volume":"44","author":"Kim","year":"2008","journal-title":"J. Pineal Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.tox.2007.04.021","article-title":"Melatonin attenuates lipopolysaccharide (LPS)-induced apoptotic liver damage in d-galactosamine-sensitized mice","volume":"237","author":"Wang","year":"2007","journal-title":"Toxicology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-079X.2011.00916.x","article-title":"Melatonin as a natural ally against oxidative stress: A physicochemical examination","volume":"51","author":"Galano","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1111\/jpi.12010","article-title":"On the free radical scavenging activities of melatonin\u2019s metabolites, AFMK and AMK","volume":"54","author":"Galano","year":"2013","journal-title":"J. Pineal Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"17920","DOI":"10.3390\/ijms151017920","article-title":"Peripheral and central effects of melatonin on blood pressure regulation","volume":"15","author":"Pechanova","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"7178","DOI":"10.1039\/c0cp02801k","article-title":"On the direct scavenging activity of melatonin towards hydroxyl and a series of peroxyl radicalsfree radical scavenging activities of melatonin\u2019s metabolites, AFMK and AMK","volume":"13","author":"Galano","year":"2011","journal-title":"Phys. Chem. Chem. Phys."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1016\/S0024-3205(03)00098-5","article-title":"Melatonin receptors and their regulation: Biochemical and structural mechanisms","volume":"72","author":"Bennett","year":"2003","journal-title":"Life Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/jpi.12241","article-title":"Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats","volume":"59","author":"Agil","year":"2015","journal-title":"J. Pineal Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cbi.2014.06.016","article-title":"Activity of melatonin against Leishmania infantum promastigotes by mitochondrial dependent pathway","volume":"220","author":"Elmahallawy","year":"2014","journal-title":"Chem. Biol. Interact."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/jpi.12147","article-title":"Melatonin improves mitochondrial function in inguinal white adipose tissue of Z\u00fccker diabetic fatty rats","volume":"57","author":"Reiter","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.nut.2012.11.005","article-title":"Antioxidant activity of melatonin in diabetes in relation to the regulation and levels of plasma Cu, Zn, Fe, Mn, and Se in Zucker diabetic fatty rats","volume":"29","author":"Agil","year":"2013","journal-title":"Nutrition"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nrn4019","article-title":"Hippoocampal insulin resistance and cognitive dysfunction","volume":"16","author":"Biessels","year":"2015","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"751","DOI":"10.2337\/dc13-1672","article-title":"Enhancement of vasoreactivity and cognition by intranasal insulin in type 2 diabetes","volume":"37","author":"Novak","year":"2014","journal-title":"Diabetes Care"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2253","DOI":"10.2337\/db14-0287","article-title":"Repurposing diabetes drugs for brain insulin resistance in Alzheimer disease","volume":"63","author":"Yarchoan","year":"2014","journal-title":"Diabetes"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1172\/JCI0216886","article-title":"Orchestrating the unfolded protein response in health and disease","volume":"110","author":"Kaufman","year":"2002","journal-title":"J. Clin. Investig."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1161\/CIRCRESAHA.110.225698","article-title":"Endoplasmic reticulum stress and inflammation in obesity and diabetes","volume":"107","author":"Hummasti","year":"2010","journal-title":"Circ. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1101\/gad.2016311","article-title":"Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis","volume":"25","author":"Guo","year":"2011","journal-title":"Gene Dev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1126\/science.1209038","article-title":"The unfolded protein response: From stress pathway to homeostatic regulation","volume":"334","author":"Walter","year":"2011","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1083\/jcb.201110131","article-title":"The impact of the unfolded protein response on human disease","volume":"197","author":"Wang","year":"2012","journal-title":"J. Cell Biol."},{"key":"ref_57","first-page":"266","article-title":"Endoplasmic reticulum stress and pancreatic beta-cell death","volume":"22","author":"Fonseca","year":"2011","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1161\/CIRCRESAHA.111.243212","article-title":"Inflammation, endoplasmic reticulum stress, autophagy, and the monocyte chemoattractant protein-1\/CCR2 pathway","volume":"110","author":"Kolattukudy","year":"2012","journal-title":"Circ. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.cmet.2012.07.005","article-title":"Thioredoxin-interacting protein mediates ER stress-induced beta cell death through initiation of the inflammasome","volume":"16","author":"Oslowski","year":"2012","journal-title":"Cell Metab."},{"key":"ref_60","first-page":"705","article-title":"Knockdown of second mitochondria-derived activator of caspase expression by RNAi enhances growth and cisplatin resistance of human lung cancer cells","volume":"25","author":"Zeng","year":"2010","journal-title":"Cancer Biother. Radiopharm."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/sj.ki.5002256","article-title":"The pathological role of Bax in cisplatin nephrotoxicity","volume":"72","author":"Wei","year":"2007","journal-title":"Kidney Int."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"43679","DOI":"10.18632\/oncotarget.6030","article-title":"5-Fluorouracil-induced RNA stress engages a TRAIL-DISC-dependent apoptosis axis facilitated by p53","volume":"6","author":"Akpinar","year":"2015","journal-title":"Oncotarget"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.lfs.2008.08.004","article-title":"Melatonin controls oxidative stress and modulates iron, ferritin, and transferrin levels in Adriamycin treated rats","volume":"83","author":"Othman","year":"2008","journal-title":"Life Sci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1111\/j.1600-079X.2009.00666.x","article-title":"Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients","volume":"46","author":"Kozakiewicz","year":"2009","journal-title":"J. Pineal Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/j.1600-079X.2010.00835.x","article-title":"Melatonin improves blood pressure, lipid profile, and parameters of oxidative stress in patients with metabolic syndrome","volume":"50","author":"Kozirog","year":"2011","journal-title":"J. Pineal Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.bbrc.2015.06.065","article-title":"Melatonin inhibits tunicamycin-induced endoplasmic reticulum stress and insulin resistance in skeletal muscle cells","volume":"463","author":"Quan","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1111\/jpi.12156","article-title":"Melatonin reduces endoplasmic reticulum stress and preserves sirtuin 1 expression in neuronal cells of newborn rats after hypoxia-ischemia","volume":"57","author":"Carloni","year":"2014","journal-title":"J. Pineal Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1111\/j.1600-079X.2011.00921.x","article-title":"Melatonin alleviates cadmium-induced cellular stress and germ cell apoptosis in testes","volume":"52","author":"Ji","year":"2012","journal-title":"J. Pineal Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.biochi.2014.05.001","article-title":"Melatonin rescues 3T3-L1 adipocytes from FFA-induced insulin resistance by inhibiting phosphorylation of IRS-1 on Ser307","volume":"103","author":"She","year":"2014","journal-title":"Biochimie"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1101\/gad.992302","article-title":"ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats","volume":"16","author":"Nishitoh","year":"2002","journal-title":"Genes Dev."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"30299","DOI":"10.1074\/jbc.M607007200","article-title":"Endoplasmic reticulum stress triggers autophagy","volume":"281","author":"Yorimitsu","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"E268","DOI":"10.1210\/jc.2010-1681","article-title":"Altered autophagy in human adipose tissues in obesity","volume":"96","author":"Kovsan","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/s13105-015-0384-1","article-title":"Autophagy regulates insulin resistance following endoplasmic reticulum stress in diabetes","volume":"71","author":"Zhang","year":"2015","journal-title":"J. Physiol. Biochem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nature09782","article-title":"Autophagy in immunity and inflammation","volume":"469","author":"Levine","year":"2011","journal-title":"Nature"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1038\/onc.2008.441","article-title":"The pivotal role of c-Jun NH2-terminal kinase-mediated Beclin 1 expression during anticancer agents-induced autophagy in cancer cells","volume":"28","author":"BLi","year":"2009","journal-title":"Oncogene"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.ceb.2009.12.004","article-title":"The role of the Atg1\/ULK1 complex in autophagy regulation","volume":"22","author":"Mizushima","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1074\/jbc.M112.412783","article-title":"XBP1 mRNA splicing triggers an autophagic response in endothelial cells through BECLIN-1 transcriptional activation","volume":"288","author":"Margariti","year":"2013","journal-title":"J. Biol. Chem."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/6\/593\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:38:39Z","timestamp":1760207919000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/6\/593"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,10]]},"references-count":77,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2017,6]]}},"alternative-id":["nu9060593"],"URL":"https:\/\/doi.org\/10.3390\/nu9060593","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,6,10]]}}}