Skip to main content
SpringerLink
Log in

Sleep Loss and the Unfolded Protein Response

  • Chapter
  • First Online:
Sleep and its Disorders

Part of the book series: Translational Medicine Research ((TRAMERE))

Abstract

Sleep loss leads to activation of the unfolded protein response (UPR) not only in the brain but also in peripheral organs (heart, lung, and pancreas). This has been shown in multiple species including mice, rats, Drosophila, and migratory birds. The unfolded protein response to sleep loss changes with age. In older mice, there is activation of the maladaptive response to sleep loss with increased expression of genes in the pro-apoptotic pathway. UPR is not simply a consequence of sleep loss but also affects sleep behavior. Alteration of the molecular machinery of the UPR alters baseline sleep as well as the degree of sleep recovery following sleep deprivation. Moreover, administration of drugs that alter the UPR can reduce the sleep fragmentation that occurs with age. UPR response to sleep loss has implications for neurodegenerative disorders and other medical conditions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ameri K, Harris AL. Activating transcription factor 4. Int J Biochem Cell Biol. 2008;40(1):14–21.

    Article  CAS  PubMed  Google Scholar 

  • Anafi RC, Pellegrino R, Shockley KR, Romer M, Tufik S, Pack AI. Sleep is not just for the brain: transcriptional responses to sleep in peripheral tissues. BMC Genomics. 2013;14:362.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asada R, Kanemoto S, Kondo S, Saito A, Imaizumi K. J Biochem. 2011;149(5):507–518. https://doi.org/10.1093/jb/mvr041

  • Ayas NT, White DP, Manson JE, Stampfer MJ, Speizer FE, Malhotra A, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003;163(2):205–9.

    Article  PubMed  Google Scholar 

  • Basseri S, Austin RC. Endoplasmic reticulum stress and lipid metabolism: mechanisms and therapeutic potential. Biochem Res Int. 2012;2012:841362.

    Article  PubMed  CAS  Google Scholar 

  • Behrman S, Acosta-Alvear D, Walter P. A CHOP-regulated microRNA controls rhodopsin expression. J Cell Biol. 2011;192(6):919–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Biswas S, Mishra P, Mallick BN. Increased apoptosis in rat brain after rapid eye movement sleep loss. Neuroscience. 2006;142(2):315–31.

    Article  CAS  PubMed  Google Scholar 

  • Bonnet MH. Effect of sleep disruption on sleep, performance, and mood. Sleep. 1985;8(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  • Brown M, Chan M, Zimmerman J, Pack A, Jackson N, Naidoo N. ER stress alters sleep and sleep homeostasis during aging. Neurobiol Aging. 2014;35(6):1431–41.

    Article  CAS  PubMed  Google Scholar 

  • Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, et al. IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. [erratum appears in Nature 2002 Nov 14;420(6912):202]. Nature. 2002;415(6867):92–6.

    Article  CAS  PubMed  Google Scholar 

  • Carskadon MA, Dement WC. Daytime sleepiness: quantification of a behavioral state. Neurosci Biobehav Rev. 1987;11(3):307–17.

    Article  CAS  PubMed  Google Scholar 

  • Chan K, Han XD, Kan YW. An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc Natl Acad Sci U S A. 2001;98(8):4611–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chee MW, Chuah LY, Venkatraman V, Chan WY, Philip P, Dinges DF. Functional imaging of working memory following normal sleep and after 24 and 35 h of sleep deprivation: correlations of fronto-parietal activation with performance. NeuroImage. 2006;31(1):419–28.

    Article  PubMed  Google Scholar 

  • Chen JC, Brunner RL, Ren H, Wassertheil-Smoller S, Larson JC, Levine DW, et al. Sleep duration and risk of ischemic stroke in postmenopausal women. Stroke. 2008;39(12):3185–92.

    Article  PubMed  PubMed Central  Google Scholar 

  • Cirelli C. How sleep deprivation affects gene expression in the brain: a review of recent findings. J Appl Physiol (1985). 2002;92(1):394–400.

    Article  CAS  Google Scholar 

  • Cirelli C, Tononi G. Gene expression in the brain across the sleep-waking cycle. Brain Res. 2000;885(2):303–21.

    Article  CAS  PubMed  Google Scholar 

  • Cirelli C, Gutierrez CM, Tononi G. Extensive and divergent effects of sleep and wakefulness on brain gene expression. Neuron. 2004;41(1):35–43.

    Article  CAS  PubMed  Google Scholar 

  • Cirelli C, Faraguna U, Tononi G. Changes in brain gene expression after long-term sleep deprivation. J Neurochem. 2006;98(5):1632–45.

    Article  CAS  PubMed  Google Scholar 

  • Colbert RA, DeLay ML, Klenk EI, Layh-Schmitt G. From HLA-B27 to spondyloarthritis: a journey through the ER. Immunol Rev. 2010;233(1):181–202.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colten HR, Altevogt BM, Institute of Medicine Committee on Sleep Medicine and Research. Sleep disorders and sleep deprivation: an unmet public health problem. Washington, DC: Institute of Medicine, National Academies Press; 2006.

    Google Scholar 

  • Connor J, Norton R, Ameratunga S, Robinson E, Civil I, Dunn R, et al. Driver sleepiness and risk of serious injury to car occupants: population based case control study. BMJ. 2002;324(7346):1125.

    Article  PubMed  PubMed Central  Google Scholar 

  • Conti B, Maier R, Barr AM, Morale MC, Lu X, Sanna PP, et al. Region-specific transcriptional changes following the three antidepressant treatments electro convulsive therapy, sleep deprivation and fluoxetine. Mol Psychiatry. 2007;12(2):167–89.

    Article  CAS  PubMed  Google Scholar 

  • Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA. Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol. 2003;23(20):7198–209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dinges D. Probing the limits of functional capability: the effects of sleep loss on short-duration tasks. In: Broughton RJ, Ogilvie RD, editors. Sleep, arousal, and performance. Boston, MA: Birkhäuser; 1992. p. 177–88.

    Google Scholar 

  • Dufey E, Sepulveda D, Rojas-Rivera D, Hetz C. Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 1. An overview. Am J Physiol Cell Physiol. 2014;307(7):C582–94.

    Article  CAS  PubMed  Google Scholar 

  • Elliott AS, Huber JD, O’Callaghan JP, Rosen CL, Miller DB. A review of sleep deprivation studies evaluating the brain transcriptome. Springerplus. 2014;3:728.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Forman MS, Lee VMY, Trojanowski JQ. ‘Unfolding’ pathways in neurodegenerative disease. Trends Neurosci. 2003;26(8):407–10.

    Article  CAS  PubMed  Google Scholar 

  • Fu Y, Li J, Lee AS. GRP78/BiP inhibits endoplasmic reticulum BIK and protects human breast cancer cells against estrogen starvation-induced apoptosis. Cancer Res. 2007;67(8):3734–40.

    Article  CAS  PubMed  Google Scholar 

  • Goel N, Rao H, Durmer JS, Dinges DF. Neurocognitive consequences of sleep deprivation. Semin Neurol. 2009;29(4):320–39.

    Article  PubMed  PubMed Central  Google Scholar 

  • Gotoh T, Mori M. Regulation of apoptosis by molecular chaperones. Tanpakushitsu Kakusan Koso. 2004;49(7 Suppl):1010–3.

    CAS  PubMed  Google Scholar 

  • Grandner MA. Addressing sleep disturbances: an opportunity to prevent cardiometabolic disease? Int Rev Psychiatry. 2014;26(2):155–76.

    Article  PubMed  PubMed Central  Google Scholar 

  • Grandner MA, Chakravorty S, Perlis ML, Oliver L, Gurubhagavatula I. Habitual sleep duration associated with self-reported and objectively determined cardiometabolic risk factors. Sleep Med. 2014;15(1):42–50.

    Article  PubMed  Google Scholar 

  • Hakim F, Wang Y, Carreras A, Hirotsu C, Zhang J, Peris E, et al. Chronic sleep fragmentation during the sleep period induces hypothalamic endoplasmic reticulum stress and PTP1b-mediated leptin resistance in male mice. Sleep. 2015;38(1):31–40.

    Article  PubMed  PubMed Central  Google Scholar 

  • Harding HP, Zhang YH, Bertolotti A, Zeng HQ, Ron D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell. 2000;5(5):897–904.

    Article  CAS  PubMed  Google Scholar 

  • Hasnain SZ, Lourie R, Das I, Chen AC, McGuckin MA. The interplay between endoplasmic reticulum stress and inflammation. Immunol Cell Biol. 2012;90(3):260–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He CH, Gong P, Hu B, Stewart D, Choi ME, Choi AM, et al. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J Biol Chem. 2001;276(24):20858–65.

    Article  CAS  PubMed  Google Scholar 

  • Healy SJ, Gorman AM, Mousavi-Shafaei P, Gupta S, Samali A. Targeting the endoplasmic reticulum-stress response as an anticancer strategy. Eur J Pharmacol. 2009;625(1–3):234–46.

    Article  CAS  PubMed  Google Scholar 

  • Heazlewood CK, Cook MC, Eri R, Price GR, Tauro SB, Taupin D, et al. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis. PLoS Med. 2008;5(3):e54.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hersey P, Zhang XD. Adaptation to ER stress as a driver of malignancy and resistance to therapy in human melanoma. Pigment Cell Melanoma Res. 2008;21(3):358–67.

    Article  CAS  PubMed  Google Scholar 

  • Hetz C, Mollereau B. Disturbance of endoplasmic reticulum proteostasis in neurodegenerative diseases. Nat Rev Neurosci. 2014;15(4):233–49.

    Article  CAS  PubMed  Google Scholar 

  • Hetz C, Martinon F, Rodriguez D, Glimcher LH. The unfolded protein response: integrating stress signals through the stress sensor IRE1alpha. Physiol Rev. 2011;91(4):1219–43.

    Article  CAS  PubMed  Google Scholar 

  • Hollien J, Weissman JS. Decay of endoplasmic reticulum-localized mRNAs during the unfolded protein response. Science. 2006;313(5783):104–7.

    Article  CAS  PubMed  Google Scholar 

  • Hotamisligil GS. Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes. Diabetes. 2005;54(Suppl 2):S73–8.

    Article  CAS  PubMed  Google Scholar 

  • Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010;140(6):900–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hu P, Han Z, Couvillon AD, Kaufman RJ, Exton JH. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol Cell Biol. 2006;26(8):3071–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huang RF, Huang SM, Lin BS, Wei JS, Liu TZ. Homocysteine thiolactone induces apoptotic DNA damage mediated by increased intracellular hydrogen peroxide and caspase 3 activation in HL-60 cells. Life Sci. 2001;68(25):2799–811.

    Article  CAS  PubMed  Google Scholar 

  • Hybiske K, Fu Z, Schwarzer C, Tseng J, Do J, Huang N, et al. Effects of cystic fibrosis transmembrane conductance regulator and DeltaF508CFTR on inflammatory response, ER stress, and Ca2+ of airway epithelia. Am J Physiol Lung Cell Mol Physiol. 2007;293(5):L1250–60.

    Article  CAS  PubMed  Google Scholar 

  • Ishii T, Itoh K, Takahashi S, Sato H, Yanagawa T, Katoh Y, et al. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem. 2000;275(21):16023–9.

    Article  CAS  PubMed  Google Scholar 

  • Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, et al. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999;13(1):76–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Johnson JA, Johnson DA, Kraft AD, Calkins MJ, Jakel RJ, Vargas MR, et al. The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann N Y Acad Sci. 2008;1147:61–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jones S, Pfister-Genskow M, Benca RM, Cirelli C. Molecular correlates of sleep and wakefulness in the brain of the white-crowned sparrow. J Neurochem. 2008;105(1):46–62.

    Article  CAS  PubMed  Google Scholar 

  • Kammoun HL, Chabanon H, Hainault I, Luquet S, Magnan C, Koike T, et al. GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice. J Clin Invest. 2009;119(5):1201–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaufman RJ. Orchestrating the unfolded protein response in health and disease. J Clin Invest. 2002;110(10):1389–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knutson KL. Does inadequate sleep play a role in vulnerability to obesity? Am J Hum Biol. 2012;24(3):361–71.

    Article  PubMed  PubMed Central  Google Scholar 

  • Knutson KL, Van Cauter E, Rathouz PJ, DeLeire T, Lauderdale DS. Trends in the prevalence of short sleepers in the USA: 1975-2006. Sleep. 2010;33(1):37–45.

    Article  PubMed  PubMed Central  Google Scholar 

  • Koh K, Evans JM, Hendricks JC, Sehgal A. A Drosophila model for age-associated changes in sleep: wake cycles. Proc Natl Acad Sci U S A. 2006;103(37):13843–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuo TH, Williams JA. Acute sleep deprivation enhances post-infection sleep and promotes survival during bacterial infection in Drosophila. Sleep. 2014;37(5):859–69.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kuo TH, Pike DH, Beizaeipour Z, Williams JA. Sleep triggered by an immune response in Drosophila is regulated by the circadian clock and requires the NFkappaB Relish. BMC Neurosci. 2010;11:17.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee AS. GRP78 induction in cancer: therapeutic and prognostic implications. Cancer Res. 2007;67(8):3496–9.

    Article  CAS  PubMed  Google Scholar 

  • Lee AS, Hendershot LM. ER stress and cancer. Cancer Biol Ther. 2006;5(7):721–2.

    Article  CAS  PubMed  Google Scholar 

  • Lee K, Tirasophon W, Shen X, Michalak M, Prywes R, Okada T, et al. IRE1-mediated unconventional mRNA splicing and S2P-mediated ATF6 cleavage merge to regulate XBP1 in signaling the unfolded protein response. Genes Dev. 2002;16(4):452–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee K, Neigeborn L, Kaufman RJ. The unfolded protein response is required for haploid tolerance in yeast. J Biol Chem. 2003;278(14):11818–27.

    Article  CAS  PubMed  Google Scholar 

  • Li J, Lee AS. Stress induction of GRP78/BiP and its role in cancer. Curr Mol Med. 2006;6(1):45–54.

    Article  CAS  PubMed  Google Scholar 

  • Ly S, Lee DA, Strus E, Prober DA, Naidoo N. Evolutionarily conserved regulation of sleep by the protein translational regulator PERK. Curr Biol. 2020;30(9):1639–48 e3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mackiewicz M, Shockley KR, Romer MA, Galante RJ, Zimmerman JE, Naidoo N, et al. Macromolecule biosynthesis: a key function of sleep. Physiol Genomics. 2007;31(3):441–57.

    Article  CAS  PubMed  Google Scholar 

  • Maret S, Dorsaz S, Gurcel L, Pradervand S, Petit B, Pfister C, et al. Homer1a is a core brain molecular correlate of sleep loss. Proc Natl Acad Sci U S A. 2007;104(50):20090–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maurel M, Chevet E, Tavernier J, Gerlo S. Getting RIDD of RNA: IRE1 in cell fate regulation. Trends Biochem Sci. 2014;39(5):245–54.

    Article  CAS  PubMed  Google Scholar 

  • McCullough KD, Martindale JL, Klotz LO, Aw TY, Holbrook NJ. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol Cell Biol. 2001;21(4):1249–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McGuckin MA, Eri RD, Das I, Lourie R, Florin TH. ER stress and the unfolded protein response in intestinal inflammation. Am J Physiol Gastrointest Liver Physiol. 2010;298(6):G820–32.

    Article  CAS  PubMed  Google Scholar 

  • Mendelson WB, Bergmann BM. Age-dependent changes in recovery sleep after 48 hours of sleep deprivation in rats. Neurobiol Aging. 2000;21(5):689–93.

    Article  CAS  PubMed  Google Scholar 

  • Mhaille AN, McQuaid S, Windebank A, Cunnea P, McMahon J, Samali A, et al. Increased expression of endoplasmic reticulum stress-related signaling pathway molecules in multiple sclerosis lesions. J Neuropathol Exp Neurol. 2008;67(3):200–11.

    Article  CAS  PubMed  Google Scholar 

  • Motohashi H, Yamamoto M. Nrf2-Keap1 defines a physiologically important stress response mechanism. Trends Mol Med. 2004;10(11):549–57.

    Article  CAS  PubMed  Google Scholar 

  • Naidoo N. Cellular stress/the unfolded protein response: relevance to sleep and sleep disorders. Sleep Med Rev. 2009;13(3):195–204.

    Article  PubMed  PubMed Central  Google Scholar 

  • Naidoo N, Giang W, Galante RJ, Pack AI. Sleep deprivation induces the unfolded protein response in mouse cerebral cortex. J Neurochem. 2005;92(5):1150–7.

    Article  CAS  PubMed  Google Scholar 

  • Naidoo N, Casiano V, Cater J, Zimmerman J, Pack AI. A role for the molecular chaperone protein BiP/GRP78 in Drosophila sleep homeostasis. Sleep. 2007;30(5):557–65.

    Article  PubMed  Google Scholar 

  • Naidoo N, Ferber M, Master M, Zhu Y, Pack AI. Aging impairs the unfolded protein response to sleep deprivation and leads to proapoptotic signaling. J Neurosci. 2008;28(26):6539–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naidoo N, Zhu J, Zhu Y, Fenik P, Lian J, Galante R, et al. Endoplasmic reticulum stress in wake-active neurons progresses with aging. Aging Cell. 2011;10(4):640–9.

    Article  CAS  PubMed  Google Scholar 

  • Naidoo N, Davis JG, Zhu J, Yabumoto M, Singletary K, Brown M, et al. Aging and sleep deprivation induce the unfolded protein response in the pancreas: implications for metabolism. Aging Cell. 2014;13(1):131–41.

    Article  CAS  PubMed  Google Scholar 

  • Nechushtan A, Smith CL, Hsu YT, Youle RJ. Conformation of the Bax C-terminus regulates subcellular location and cell death. EMBO J. 1999;18(9):2330–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen DT, Kebache S, Fazel A, Wong HN, Jenna S, Emadali A, et al. Nck-dependent activation of extracellular signal-regulated kinase-1 and regulation of cell survival during endoplasmic reticulum stress. Mol Biol Cell. 2004;15(9):4248–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Okada T, Yoshida H, Akazawa R, Negishi M, Mori K. Distinct roles of activating transcription factor 6 (ATF6) and double-stranded RNA-activated protein kinase-like endoplasmic reticulum kinase (PERK) in transcription during the mammalian unfolded protein response. Biochem J. 2002;366(Pt 2):585–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Outinen PA, Sood SK, Pfeifer SI, Pamidi S, Podor TJ, Li J, et al. Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells. Blood. 1999;94(3):959–67.

    Article  CAS  PubMed  Google Scholar 

  • Pirot P, Naamane N, Libert F, Magnusson NE, Orntoft TF, Cardozo AK, et al. Global profiling of genes modified by endoplasmic reticulum stress in pancreatic beta cells reveals the early degradation of insulin mRNAs. Diabetologia. 2007;50(5):1006–14.

    Article  CAS  PubMed  Google Scholar 

  • Pyrko P, Schonthal AH, Hofman FM, Chen TC, Lee AS. The unfolded protein response regulator GRP78/BiP as a novel target for increasing chemosensitivity in malignant gliomas. Cancer Res. 2007;67(20):9809–16.

    Article  CAS  PubMed  Google Scholar 

  • Qureshi AI, Giles WH, Croft JB, Bliwise DL. Habitual sleep patterns and risk for stroke and coronary heart disease: a 10-year follow-up from NHANES I. Neurology. 1997;48(4):904–11.

    Article  CAS  PubMed  Google Scholar 

  • Rao RV, Peel A, Logvinova A, del Rio G, Hermel E, Yokota T, et al. Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett. 2002;514(2–3):122–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reddy PH, Williams M, Tagle DA. Recent advances in understanding the pathogenesis of Huntington’s disease. Trends Neurosci. 1999;22(6):248–55.

    Article  CAS  PubMed  Google Scholar 

  • Reddy RK, Mao C, Baumeister P, Austin RC, Kaufman RJ, Lee AS. Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation. J Biol Chem. 2003;278(23):20915–24.

    Article  CAS  PubMed  Google Scholar 

  • Ron D. Hyperhomocysteinemia and function of the endoplasmic reticulum. J Clin Invest. 2001;107(10):1221–2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ron D. Translational control in the endoplasmic reticulum stress response. J Clin Invest. 2002;110(10):1383–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rumpf RC, Pazos JJ. Optimization of planar self-collimating photonic crystals. J Opt Soc Am A Opt Image Sci Vis. 2013;30(7):1297–304.

    Article  PubMed  Google Scholar 

  • Santos CX, Tanaka LY, Wosniak J, Laurindo FR. Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase. Antioxid Redox Signal. 2009;11(10):2409–27.

    Article  CAS  PubMed  Google Scholar 

  • Scheper W, Hoozemans JJ. The unfolded protein response in neurodegenerative diseases: a neuropathological perspective. Acta Neuropathol. 2015;130(3):315–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaw PJ, Cirelli C, Greenspan RJ, Tononi G. Correlates of sleep and waking in Drosophila melanogaster. Science. 2000a;287(5459):1834–7.

    Article  CAS  PubMed  Google Scholar 

  • Shaw MK, He CY, Roos DS, Tilney LG. Proteasome inhibitors block intracellular growth and replication of Toxoplasma gondii. Parasitology. 2000b;121(Pt 1):35–47.

    Article  CAS  PubMed  Google Scholar 

  • Shiromani PJ, Lu J, Wagner D, Thakkar J, Greco MA, Basheer R, et al. Compensatory sleep response to 12 h wakefulness in young and old rats. Am J Physiol Regul Integr Comp Physiol. 2000;278(1):R125–33.

    Article  CAS  PubMed  Google Scholar 

  • Spiegel K, Knutson K, Leproult R, Tasali E, Van Cauter E. Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. J Appl Physiol (1985). 2005;99(5):2008–19.

    Article  CAS  Google Scholar 

  • Terao A, Steininger TL, Hyder K, Apte-Deshpande A, Ding J, Rishipathak D, et al. Differential increase in the expression of heat shock protein family members during sleep deprivation and during sleep. Neuroscience. 2003;116(1):187–200.

    Article  CAS  PubMed  Google Scholar 

  • Terao A, Wisor JP, Peyron C, Apte-Deshpande A, Wurts SW, Edgar DM, et al. Gene expression in the rat brain during sleep deprivation and recovery sleep: an Affymetrix GeneChip study. Neuroscience. 2006;137(2):593–605.

    Article  CAS  PubMed  Google Scholar 

  • Ulmer CS, Calhoun PS, Edinger JD, Wagner HR, Beckham JC. Sleep disturbance and baroreceptor sensitivity in women with posttraumatic stress disorder. J Trauma Stress. 2009;22(6):643–7.

    Article  PubMed  PubMed Central  Google Scholar 

  • Upton JP, Wang L, Han D, Wang ES, Huskey NE, Lim L, et al. IRE1alpha cleaves select microRNAs during ER stress to derepress translation of proapoptotic Caspase-2. Science. 2012;338(6108):818–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Urano F, Bertolotti A, Ron D. IRE1 and efferent signaling from the endoplasmic reticulum. J Cell Sci. 2000;113(Pt 21):3697–702.

    Article  CAS  PubMed  Google Scholar 

  • Vandewynckel YP, Laukens D, Geerts A, Bogaerts E, Paridaens A, Verhelst X, et al. The paradox of the unfolded protein response in cancer. Anticancer Res. 2013;33(11):4683–94.

    CAS  PubMed  Google Scholar 

  • Venugopal R, Jaiswal AK. Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H: quinone oxidoreductase1 gene. Proc Natl Acad Sci U S A. 1996;93(25):14960–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walter P, Ron D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011;334(6059):1081–6.

    Article  CAS  PubMed  Google Scholar 

  • Wang M, Kaufman RJ. The impact of the endoplasmic reticulum protein-folding environment on cancer development. Nat Rev Cancer. 2014;14(9):581–97.

    Article  CAS  PubMed  Google Scholar 

  • Welsh DK, Richardson GS, Dement WC. Effect of age on the circadian pattern of sleep and wakefulness in the mouse. J Gerontol. 1986;41(5):579–86.

    Article  CAS  PubMed  Google Scholar 

  • Williams JA, Sathyanarayanan S, Hendricks JC, Sehgal A. Interaction between sleep and the immune response in Drosophila: a role for the NFkappaB relish. Sleep. 2007;30(4):389–400.

    Article  PubMed  Google Scholar 

  • Yoshida H, Haze K, Yanagi H, Yura T, Mori K. Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins. Involvement of basic leucine zipper transcription factors. [erratum appears in J Biol Chem 1999 Jan 22;274(4):2592]. J Biol Chem. 1998;273(50):33741–9.

    Article  CAS  PubMed  Google Scholar 

  • Yoshida H, Matsui T, Yamamoto A, Okada T, Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell. 2001;107(7):881–91.

    Article  CAS  PubMed  Google Scholar 

  • Yoshida H, Matsui T, Hosokawa N, Kaufman RJ, Nagata K, Mori K. A time-dependent phase shift in the mammalian unfolded protein response. Dev Cell. 2003;4(2):265–71.

    Article  CAS  PubMed  Google Scholar 

  • Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008;454(7203):455–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang LH, Zhang X. Roles of GRP78 in physiology and cancer. J Cell Biochem. 2010;110(6):1299–305.

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Cai Y, Adachi MT, Oshiro S, Aso T, Kaufman RJ, et al. Homocysteine induces programmed cell death in human vascular endothelial cells through activation of the unfolded protein response. J Biol Chem. 2001;276(38):35867–74.

    Article  CAS  PubMed  Google Scholar 

  • Zhu Y, Fenik P, Zhan G, Sanfillipo-Cohn B, Naidoo N, Veasey SC. Eif-2a protects brainstem motoneurons in a murine model of sleep apnea. J Neurosci. 2008;28(9):2168–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Thanks to Sarah Ly for helpful comments and edits during the writing of the manuscript and Michael Paolini for assistance with figures. This study was supported by NIH/AG17628.

Author information

Authors and Affiliations

  1. Division of Sleep Medicine, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Nirinjini Naidoo

Authors
  1. Nirinjini Naidoo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nirinjini Naidoo .

Editor information

Editors and Affiliations

  1. John Miclot Professor, Division of Sleep Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Allan I. Pack

  2. Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China

    Qing Yun Li

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature B.V. and Shanghai Jiao Tong University Press

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Naidoo, N. (2022). Sleep Loss and the Unfolded Protein Response. In: Pack, A.I., Li, Q.Y. (eds) Sleep and its Disorders. Translational Medicine Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-2168-2_7

Download citation

Publish with us

Policies and ethics

Search

Navigation