Heat shock protein 70.1 (Hsp70.1) affects neuronal cell fate by regulating lysosomal acid sphingomyelinase.

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  • Author(s): Zhu H;Zhu H; Yoshimoto T; Yoshimoto T; Yamashima T; Yamashima T
  • Source:
    The Journal of biological chemistry [J Biol Chem] 2014 Oct 03; Vol. 289 (40), pp. 27432-43. Date of Electronic Publication: 2014 Jul 29.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
    • Publication Information:
      Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology
      Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
    • Subject Terms:
    • Abstract:
      The inducible expression of heat shock protein 70.1 (Hsp70.1) plays cytoprotective roles in its molecular chaperone function. Binding of Hsp70 to an endolysosomal phospholipid, bis(monoacylglycero)phosphate (BMP), has been recently shown to stabilize lysosomal membranes by enhancing acid sphingomyelinase (ASM) activity in cancer cells. Using the monkey experimental paradigm, we have reported that calpain-mediated cleavage of oxidized Hsp70.1 causes neurodegeneration in the hippocampal cornu ammonis 1 (CA1), whereas expression of Hsp70.1 in the motor cortex without calpain activation contributes to neuroprotection. However, the molecular mechanisms of the lysosomal destabilization/stabilization determining neuronal cell fate have not been elucidated. To elucidate whether regulation of lysosomal ASM could affect the neuronal fate, we analyzed Hsp70.1-BMP binding and ASM activity by comparing the motor cortex and the CA1. We show that Hsp70.1 being localized at the lysosomal membrane, lysosomal lipid BMP levels, and the lipid binding domain of Hsp70.1 are crucial for Hsp70.1-BMP binding. In the postischemic motor cortex, Hsp70.1 being localized at the lysosomal membrane could bind to BMP without calpain activation and decreased BMP levels, resulting in increasing ASM activity and lysosomal stability. However, in the postischemic CA1, calpain activation and a concomitant decrease in the lysosomal membrane localization of Hsp70.1 and BMP levels may diminish Hsp70.1-BMP binding, resulting in decreased ASM activity and lysosomal rupture with leakage of cathepsin B into the cytosol. A TUNEL assay revealed the differential neuronal vulnerability between the CA1 and the motor cortex. These results suggest that regulation of ASM activation in vivo by Hsp70.1-BMP affects lysosomal stability and neuronal survival or death after ischemia/reperfusion.
      (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)
    • References:
      Exp Neurol. 2001 Jul;170(1):27-35. (PMID: 11421581)
      J Biol Chem. 2011 Feb 4;286(5):3777-88. (PMID: 21098024)
      Eur J Neurosci. 1996 Sep;8(9):1932-44. (PMID: 8921284)
      J Biol Chem. 1993 Nov 25;268(33):25239-43. (PMID: 8227089)
      Annu Rev Cell Dev Biol. 2005;21:81-103. (PMID: 16212488)
      J Neurochem. 2012 Feb;120(4):477-94. (PMID: 22118687)
      BMC Neurosci. 2009 Sep 03;10:111. (PMID: 19725984)
      Biol Chem. 2001 Feb;382(2):283-90. (PMID: 11308026)
      Prostaglandins Leukot Essent Fatty Acids. 2009 Nov-Dec;81(5-6):313-24. (PMID: 19857945)
      Eur J Neurosci. 1998 May;10(5):1723-33. (PMID: 9751144)
      Cell Cycle. 2010 Jun 15;9(12):2305-9. (PMID: 20519957)
      Biochem Biophys Res Commun. 2010 Mar 19;393(4):806-11. (PMID: 20171158)
      Nature. 2013 Oct 17;502(7471):312-3. (PMID: 24089207)
      Free Radic Biol Med. 2009 Jun 1;46(11):1472-7. (PMID: 19272443)
      Blood Cells Mol Dis. 2008 May-Jun;40(3):420-7. (PMID: 18054258)
      J Neurochem. 2012 Feb;120(4):574-85. (PMID: 22017466)
      J Biol Chem. 2001 Feb 23;276(8):5760-8. (PMID: 11104761)
      J Lipid Res. 2012 Sep;53(9):1823-31. (PMID: 22750654)
      Cell Calcium. 2004 Sep-Oct;36(3-4):285-93. (PMID: 15261484)
      Am J Pathol. 2009 May;174(5):1891-909. (PMID: 19349362)
      J Lipid Res. 2009 Feb;50(2):243-55. (PMID: 18809971)
      Brain Res. 1998 Apr 20;790(1-2):1-13. (PMID: 9593800)
      Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6458-63. (PMID: 8692837)
      Curr Mol Med. 2010 Jul;10(5):454-66. (PMID: 20540705)
      J Biol Chem. 1998 Jul 17;273(29):18250-9. (PMID: 9660788)
      Free Radic Biol Med. 2006 Feb 1;40(3):376-87. (PMID: 16443152)
      Prog Neurobiol. 2000 Oct;62(3):273-95. (PMID: 10840150)
      Biochim Biophys Acta. 2009 Apr;1793(4):746-54. (PMID: 18948147)
      J Exp Med. 2004 Aug 16;200(4):425-35. (PMID: 15314073)
      Mol Cancer Ther. 2013 Oct;12(10):2018-30. (PMID: 23920274)
      Prog Neurobiol. 2009 Dec;89(4):343-58. (PMID: 19772886)
      Curr Protoc Cell Biol. 2011 Sep;Chapter 4:Unit4.19. (PMID: 21898338)
      Nature. 1998 Mar 12;392(6672):193-7. (PMID: 9515966)
      J Neurosci. 1994 Jun;14(6):3934-44. (PMID: 8207497)
      Neuroscience. 2013 Oct 10;250:394-407. (PMID: 23872392)
      Antioxid Redox Signal. 2010 Mar;12(3):327-36. (PMID: 19686046)
      Subcell Biochem. 2008;49:241-68. (PMID: 18751914)
      Nature. 2010 Jan 28;463(7280):549-53. (PMID: 20111001)
      Biochim Biophys Acta. 1993 Mar 5;1162(1-2):171-6. (PMID: 8448181)
      Biochim Biophys Acta. 2014 May;1838(5):1344-61. (PMID: 24480410)
      J Neurochem. 1996 Jan;66(1):421-4. (PMID: 8522983)
      Prog Neurobiol. 2010 Oct;92(2):184-211. (PMID: 20685377)
      Cancer Cell. 2013 Sep 9;24(3):379-93. (PMID: 24029234)
    • Contributed Indexing:
      Keywords: Brain; Calpain; Cell Death; Ceramide; Lysosome; Neurodegeneration
    • Accession Number:
      0 (HSP70 Heat-Shock Proteins)
      0 (Lysophospholipids)
      0 (Monoglycerides)
      0 (bis(monoacylglyceryl)phosphate)
      0 (heat-shock protein 70.1)
      EC 3.1.4.12 (Sphingomyelin Phosphodiesterase)
    • Publication Date:
      Date Created: 20140731 Date Completed: 20141217 Latest Revision: 20240508
    • Publication Date:
      20240508
    • Accession Number:
      PMC4183783
    • Accession Number:
      10.1074/jbc.M114.560334
    • Accession Number:
      25074941