Skip to main content

Advertisement

SpringerLink
Log in

The functional role of stress proteins in ER stress mediated cell death

  • Review article
  • Published:
Anatomical Science International Aims and scope Submit manuscript

Abstract

The endoplasmic reticulum (ER) is an intracellular organelle involved in biosynthesis and the secretory pathway. This organelle has many resident proteins including biosynthetic enzymes and secretory proteins. Recent studies have suggested that dysfunction of the ER or secretory pathway is involved in the pathogenesis of various human diseases. Some stresses acting on the ER, which are designated ER stress, induce the accumulation of unfolded/misfolded proteins in the ER, leading to cell death. Misfolded proteins are retained until they form their native conformation or returned to the cytosol for degradation by the proteasome. Among the ER-resident proteins, molecular chaperones prevent aggregation of proteins within the ER, and orchestrate the ER quality control systems. We have reported the roles of novel stress proteins, namely 150-kDa oxygen-regulated protein, 94-kDa glucose-regulated protein and RA410. These proteins are induced significantly by hypoxia or oxidative stress and have cytoprotective effects under these conditions. These findings suggest that hypoxia and oxidative stress target the ER and secretory pathway, resulting in ER stress, and that these proteins exert cytoprotective effects in various diseases associated with ER stress.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  • Aleshin AN, Sawa Y, Kitagawa-Sakakida S et al (2005) 150-kDa oxygen-regulated protein attenuates myocardial ischemia-reperfusion injury in rat heart. J Mol Cell Cardiol 38(3):517–525

    Article  PubMed  CAS  Google Scholar 

  • Bando Y, Ogawa S, Yamauchi A et al (2000) 150-kDa oxygen-regulated protein (ORP150) functions as a novel molecular chaperone in MDCK cells. Am J Physiol Cell Physiol 278(6):C1172–C1182

    PubMed  CAS  Google Scholar 

  • Bando Y, Katayama T, Kasai K, Taniguchi M, Tamatani M, Tohyama M (2003) GRP94 (94 kDa glucose-regulated protein) suppresses ischemic neuronal cell death against ischemia/reperfusion injury. Eur J Neurosci 18(4):829–840

    Article  PubMed  Google Scholar 

  • Bando Y, Katayama T, Aleshin AN, Manabe T, Tohyama M (2004a) GRP94 reduces cell death in SH-SY5Y cells perturbated calcium homeostasis. Apoptosis 9(4):501–508

    Article  PubMed  CAS  Google Scholar 

  • Bando Y, Tsukamoto Y, Katayama T et al (2004b) ORP150/HSP12A protects renal tubular epithelium from ischemia-induced cell death. FASEB J 18(12):1401–1403

    PubMed  CAS  Google Scholar 

  • Bando Y, Katayama T, Taniguchi M et al (2005a) RA410/Sly1 suppresses MPP+ and 6-hydroxydopamine-induced cell death in SH-SY5Y cells. Neurobiol Dis 18(1):143–151

    Article  PubMed  CAS  Google Scholar 

  • Bando Y, Onuki R, Katayama T et al (2005b) Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal degeneration in Parkinson’s disease and Huntington’s disease. Neurochem Int 46(1):11–18

    Article  PubMed  CAS  Google Scholar 

  • Eletto D, Dersh D, Argon Y (2010) GRP94 in ER quality control and stress responses. Semin Cell Dev Biol 21(5):479–485

    Article  PubMed  CAS  Google Scholar 

  • Harding HP, Zhang Y, Ron D (1999) Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397(6716):271–274

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Haze K, Yoshida H, Yanagi H, Yura T, Mori K (1999) Mammalian transcription factor ATF6 is synthesized as a transmembrane protein and activated by proteolysis in response to endoplasmic reticulum stress. Mol Biol Cell 10(11):3787–3799

    PubMed  CAS  Google Scholar 

  • Honma Y, Kanazawa K, Mori T et al (1999) Identification of a novel gene, OASIS, which encodes for a putative CREB/ATF family transcription factor in the long-term cultured astrocytes and gliotic tissue. Brain Res Mol Brain Res 69(1):93–103

    Article  PubMed  CAS  Google Scholar 

  • Hoseki J, Ushioda R, Nagata K (2010) Mechanism and components of endoplasmic reticulum-associated degradation. J Biochem 147(1):19–25

    Article  PubMed  CAS  Google Scholar 

  • Hosokawa N, Wada I, Hasegawa K et al (2001) A novel ER alpha-mannosidase-like protein accelerates ER-associated degradation. EMBO Rep 2(5):415–422

    PubMed  CAS  Google Scholar 

  • Imaizumi K, Katayama T, Tohyama M (2001a) Presenilin and the UPR. Nat Cell Biol 3(5):E104

    Article  PubMed  CAS  Google Scholar 

  • Imaizumi K, Miyoshi K, Katayama T et al (2001b) The unfolded protein response and Alzheimer’s disease. Biochim Biophys Acta 1536(2–3):85–96

    PubMed  CAS  Google Scholar 

  • Katayama T, Imaizumi K, Manabe T, Hitomi J, Kudo T, Tohyama M (2004) Induction of neuronal death by ER stress in Alzheimer’s disease. J Chem Neuroanat 28(1–2):67–78

    Article  PubMed  CAS  Google Scholar 

  • Kaufman RJ (2002) Orchestrating the unfolded protein response in health and disease. J Clin Investig 110:1389–1398

    PubMed  CAS  Google Scholar 

  • Kitao Y, Ozawa K, Miyazaki M et al (2001) Expression of the endoplasmic reticulum molecular chaperone (ORP150) rescues hippocampal neurons from glutamate toxicity. J Clin Invest 108(10):1439–1450

    PubMed  CAS  Google Scholar 

  • Kondo S, Murakami T, Tatsumi K et al (2005) OASIS, a CREB/ATF-family member, modulates UPR signalling in astrocytes. Nat Cell Biol 7(2):186–194

    Article  PubMed  CAS  Google Scholar 

  • Kuwabara K, Matsumoto M, Ikeda J et al (1996) Purification and characterization of a novel stress protein, the 150-kDa oxygen-regulated protein (ORP150), from cultured rat astrocytes and its expression in ischemic mouse brain. J Biol Chem 271(9):5025–5032

    Article  PubMed  CAS  Google Scholar 

  • Machamer CE (2003) Golgi disassembly in apoptosis: cause or effect? Trends Cell Biol 13:279–281

    Article  PubMed  CAS  Google Scholar 

  • Mancini M, Machamer CE, Roy S et al (2000) Caspase-2 is localized at the Golgi complex and cleaves golgin-160 during apoptosis. J Cell Biol 149(3):603–612

    Article  PubMed  CAS  Google Scholar 

  • Matsuo N, Ogawa S, Takagi T et al (1997) Cloning of a putative vesicle transport-related protein, RA410, from cultured rat astrocytes and its expression in ischemic rat brain. J Biol Chem 272(26):16438–16444

    Article  PubMed  CAS  Google Scholar 

  • Miyazaki M, Ozawa K, Hori O et al (2002) Expression of 150-kd oxygen-regulated protein in the hippocampus suppresses delayed neuronal cell death. J Cereb Blood Flow Metab 22(8):979–987

    Article  PubMed  CAS  Google Scholar 

  • Murakami T, Saito A, Hino S et al (2009) Signalling mediated by the endoplasmic reticulum stress transducer OASIS is involved in bone formation. Nat Cell Biol 11(10):1205–1211

    Article  PubMed  CAS  Google Scholar 

  • Nakatani Y, Kaneto H, Kawamori D et al (2005) Involvement of endoplasmic reticulum stress in insulin resistance and diabetes. J Biol Chem 280(1):847–851

    PubMed  CAS  Google Scholar 

  • Nakatani Y, Kaneto H, Hatazaki M et al (2006) Increased stress protein ORP150 autoantibody production in Type 1 diabetic patients. Diabet Med 23(2):216–219

    Article  PubMed  CAS  Google Scholar 

  • Onuki R, Bando Y, Suyama E et al (2004) An RNA-dependent protein kinase is involved in tunicamycin-induced apoptosis and Alzheimer’s disease. EMBO J 23(4):959–968

    Article  PubMed  CAS  Google Scholar 

  • Ozawa K, Kuwabara K, Tamatani M et al (1999) 150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic cell death. J Biol Chem 274(10):6397–6404

    Article  PubMed  CAS  Google Scholar 

  • Ozawa K, Tsukamoto Y, Hori O et al (2001a) Regulation of tumor angiogenesis by oxygen-regulated protein 150, an inducible endoplasmic reticulum chaperone. Cancer Res 61(10):4206–4213

    PubMed  CAS  Google Scholar 

  • Ozawa K, Kondo T, Hori O et al (2001b) Expression of the oxygen-regulated protein ORP150 accelerates wound healing by modulating intracellular VEGF transport. J Clin Invest 108(1):41–50

    PubMed  CAS  Google Scholar 

  • Ozawa K, Miyazaki M, Matsuhisa M et al (2005) The endoplasmic reticulum chaperone improves insulin resistance in type 2 diabetes. Diabetes 54(3):657–663

    Article  PubMed  CAS  Google Scholar 

  • Ron D (2002) Translational control in the endoplasmic reticulum stress response. J Clin Invest 110(10):1383–1388

    PubMed  CAS  Google Scholar 

  • Sanson M, Augé N, Vindis C et al (2009) Oxidized low-density lipoproteins trigger endoplasmic reticulum stress in vascular cells: prevention by oxygen-regulated protein 150 expression. Circ Res 104(3):328–336

    Article  PubMed  CAS  Google Scholar 

  • Tamatani M, Matsuyama T, Yamaguchi A et al (2001) ORP150 protects against hypoxia/ischemia-induced neuronal death. Nat Med 7(3):317–323

    Article  PubMed  CAS  Google Scholar 

  • Tsukamoto Y, Kuwabara K, Hirota S et al (1996) 150-kD oxygen-regulated protein is expressed in human atherosclerotic plaques and allows mononuclear phagocytes to withstand cellular stress on exposure to hypoxia and modified low density lipoprotein. J Clin Invest 98(8):1930–1941

    Article  PubMed  CAS  Google Scholar 

  • Tsukamoto Y, Kuwabara K, Hirota S et al (1998) Expression of the 150-kd oxygen-regulated protein in human breast cancer. Lab Invest 78(6):699–706

    PubMed  CAS  Google Scholar 

  • Wang XZ, Harding HP, Zhang Y, Jolicoeur EM, Kuroda M, Ron D (1998) Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J 17(19):5708–5717

    Article  PubMed  CAS  Google Scholar 

  • Yoshida H, Haze K, Yanagi H, Yura T, Mori K (1998) 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. J Biol Chem 273(50):33741–33749

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I greatly thank Prof. Masaya Tohyama (Osaka University Graduate School of Medicine) and Dr. Satoshi Ogawa for their advice and valuable discussions. I also thank Profs. Shigetaka Yoshida (Asahikawa Medical University) and Taiichi Katayama (United Graduate School of Child Development, Osaka University, Kanazawa University and Hamamatsu University Graduate School of Medicine) for their helpful discussions. This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Conflict of interest

The author reports no financial or any other conflicts of interest with the contents of the manuscript.

Author information

Authors and Affiliations

  1. Department of Functional Anatomy and Neuroscience, Asahikawa Medical University, Asahikawa, 078-8510, Japan

    Yoshio Bando

Authors
  1. Yoshio Bando
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yoshio Bando.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bando, Y. The functional role of stress proteins in ER stress mediated cell death. Anat Sci Int 87, 14–23 (2012). https://doi.org/10.1007/s12565-011-0127-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12565-011-0127-5

Keywords

Search

Navigation