Home LiteratureArticle Details
PMID: 16237177 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, U.S. Gov't, P.H.S.

Extracellular heat shock protein 70: a critical component for motoneuron survival.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 25 ·No. 42 ·2005-10-19 ·Pages 9735-45

Robinson MB, Tidwell JL, Gould T, Taylor AR, Newbern JM, Graves J, Tytell M, Milligan CE

Abstract

The dependence of developing spinal motoneuron survival on a soluble factor(s) from their target, muscle tissue is well established both in vivo and in vitro. Considering this apparent dependence, we examined whether a specific component of the stress response mediates motoneuron survival in trophic factor-deprived environments. We demonstrate that, although endogenous expression of heat shock protein 70 (HSP70) did not change during trophic factor deprivation, application of e-rhHsp70 (exogenous recombinant human Hsp70) promoted motoneuron survival. Conversely, depletion of HSP70 from chick muscle extract (MEx) potently reduces the survival-promoting activity of MEx. Additionally, exogenous treatment with or spinal cord overexpression of Hsp70 enhances motoneuron survival in vivo during the period of naturally occurring cell death [programmed cell death (PCD)]. Hindlimb muscle cells and lumbar spinal astrocytes readily secrete HSP70 in vitro, suggesting potential physiological sources of extracellular Hsp70 for motoneurons. However, in contrast to exogenous treatment with or overexpression of Hsp70 in vivo, muscle-targeted injections of this factor in an ex vivo preparation fail to attenuate motoneuron PCD. These data (1) suggest that motoneuron survival requirements may extend beyond classical trophic factors to include HSP70, (2) indicate that the source of this factor is instrumental in determining its trophic function, and (3) may therefore influence therapeutic strategies designed to increase motoneuron Hsp70 signaling during disease or injury.

MeSH Terms
Animals Cell Death/physiology Cell Survival/physiology Cells, Cultured Chick Embryo Extracellular Fluid/cytology,physiology HSP70 Heat-Shock Proteins/physiology Motor Neurons/cytology,physiology
Chemicals
HSP70 Heat-Shock Proteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Robinson Mac B
Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Tidwell J Lille
Gould Thomas
Taylor Anna R
Newbern Jason M
Graves Jason
Tytell Michael
Milligan Carol E
References (72)
72 references, click to expand
  1. Heat-shock protein protection.
    Trends Neurosci. 1999 Mar;22(3):97-9 PMID: 10199631
  2. A controlled trial of recombinant methionyl human BDNF in ALS: The BDNF Study Group (Phase III).
    Neurology. 1999 Apr 22;52(7):1427-33 PMID: 10227630
  3. Heat shock protein 70 and ATP as partners in cell homeostasis (Review).
    Int J Mol Med. 1999 Nov;4(5):463-74 PMID: 10534567
  4. The neuroprotective potential of heat shock protein 70 (HSP70).
    Mol Med Today. 1999 Dec;5(12):525-31 PMID: 10562718
  5. HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine.
    Nat Med. 2000 Apr;6(4):435-42 PMID: 10742151
  6. Mice overexpressing rat heat shock protein 70 are protected against cerebral infarction.
    Ann Neurol. 2000 Jun;47(6):782-91 PMID: 10852544
  7. Glial cell line-derived neurotrophic factor and developing mammalian motoneurons: regulation of programmed cell death among motoneuron subtypes.
    J Neurosci. 2000 Jul 1;20(13):5001-11 PMID: 10864958
  8. Heat-shock protein 70 inhibits apoptosis by preventing recruitment of procaspase-9 to the Apaf-1 apoptosome.
    Nat Cell Biol. 2000 Aug;2(8):469-75 PMID: 10934466
  9. Negative regulation of the Apaf-1 apoptosome by Hsp70.
    Nat Cell Biol. 2000 Aug;2(8):476-83 PMID: 10934467
  10. Characterization of the execution pathway of developing motoneurons deprived of trophic support.
    J Neurobiol. 2001 Mar;46(4):249-64 PMID: 11180153
  11. Retinal uptake of intravitreally injected Hsc/Hsp70 and its effect on susceptibility to light damage.
    Mol Vis. 2001 Mar 07;7:48-56 PMID: 11239246
  12. In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance.
    Brain Res. 2001 Sep 28;914(1-2):66-73 PMID: 11578598
  13. Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR) 2 and TLR4.
    J Biol Chem. 2002 Apr 26;277(17):15028-34 PMID: 11836257
  14. The effect of neonatal nerve injury on the expression of heat shock proteins in developing rat motoneurones.
    J Neurotrauma. 2002 May;19(5):667-79 PMID: 12042100
  15. Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70.
    Eur J Neurosci. 2002 May;15(10):1646-54 PMID: 12059972
  16. Chaperoning signaling pathways: molecular chaperones as stress-sensing 'heat shock' proteins.
    J Cell Sci. 2002 Jul 15;115(Pt 14):2809-16 PMID: 12082142
  17. Elucidating the molecular mechanisms that underlie the target control of motoneuron death.
    Int J Dev Biol. 2002;46(4):551-8 PMID: 12141443
  18. Circulating heat shock protein and heat shock protein antibody levels in established hypertension.
    J Hypertens. 2002 Sep;20(9):1815-20 PMID: 12195124
  19. CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes.
    J Cell Biol. 2002 Sep 30;158(7):1277-85 PMID: 12356871
  20. Exercise induces hepatosplanchnic release of heat shock protein 72 in humans.
    J Physiol. 2002 Nov 1;544(3):957-62 PMID: 12411538
  21. Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release.
    J Biol Chem. 2003 Jun 13;278(24):21601-6 PMID: 12682040
  22. High threshold for induction of the stress response in motor neurons is associated with failure to activate HSF1.
    J Neurosci. 2003 Jul 2;23(13):5789-98 PMID: 12843283
  23. Accumulation of major stress protein 70kDa protects myeloid and lymphoid cells from death by apoptosis.
    Apoptosis. 1997;2(2):156-63 PMID: 14646550
  24. The function of neurotrophic factor receptors expressed by the developing adductor motor pool in vivo.
    J Neurosci. 2004 May 12;24(19):4668-82 PMID: 15140938
  25. Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration.
    Cell Stress Chaperones. 2004 Mar;9(1):88-98 PMID: 15270081
  26. Hop: more than an Hsp70/Hsp90 adaptor protein.
    Bioessays. 2004 Oct;26(10):1058-68 PMID: 15382137
  27. Interaction of the Hsp90 cochaperone cyclophilin 40 with Hsc70.
    Cell Stress Chaperones. 2004 Summer;9(2):167-81 PMID: 15497503
  28. Hsp70 mutant proteins modulate additional apoptotic pathways and improve cell survival.
    Cell Stress Chaperones. 2004 Autumn;9(3):229-42 PMID: 15544161
  29. Downstream caspases are novel targets for the antiapoptotic activity of the molecular chaperone hsp70.
    Cell Stress Chaperones. 2004 Autumn;9(3):265-75 PMID: 15544164
  30. Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain injury.
    J Cereb Blood Flow Metab. 2005 Jul;25(7):899-910 PMID: 15744251
  31. Heat shock protein 90 and heat shock protein 70 are components of dengue virus receptor complex in human cells.
    J Virol. 2005 Apr;79(8):4557-67 PMID: 15795242
  32. Expression of heat shock genes (hsp70) in the mammalian nervous system.
    Results Probl Cell Differ. 1991;17:217-29 PMID: 1803421
  33. Different populations of dorsal lateral geniculate nucleus neurons have concentration-specific requirements for a cortically derived neuron survival factor.
    Exp Neurol. 1990 Dec;110(3):284-90 PMID: 2249738
  34. Effect of heat shock proteins on survival of isolated aortic cells from normal and atherosclerotic cynomolgus macaques.
    Atherosclerosis. 1990 Oct;84(2-3):111-9 PMID: 2282091
  35. The dependence of motoneurons on their target muscle during postnatal development of the mouse.
    J Neurosci. 1990 May;10(5):1643-53 PMID: 2332802
  36. Factors influencing astrocyte growth and development in defined media.
    Int J Dev Neurosci. 1984;2(6):575-84 PMID: 24874398
  37. The heat-shock proteins.
    Annu Rev Genet. 1988;22:631-77 PMID: 2853609
  38. Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins.
    J Cell Physiol. 1989 Feb;138(2):257-66 PMID: 2918030
  39. Reduction of naturally occurring motoneuron death in vivo by a target-derived neurotrophic factor.
    Science. 1988 May 13;240(4854):919-22 PMID: 3363373
  40. Muscle-derived factors that support survival and promote fiber outgrowth from embryonic chick spinal motor neurons in culture.
    Dev Biol. 1986 Nov;118(1):209-21 PMID: 3770299
  41. Heat shock-like protein is transferred from glia to axon.
    Brain Res. 1986 Jan 15;363(1):161-4 PMID: 3947949
  42. Rapid purification of mammalian 70,000-dalton stress proteins: affinity of the proteins for nucleotides.
    Mol Cell Biol. 1985 Jun;5(6):1229-37 PMID: 4033650
  43. A unifying hypothesis for the cause of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer disease.
    Ann Neurol. 1981 Dec;10(6):499-505 PMID: 6173010
  44. Cell death of motoneurons in the chick embryo spinal cord. II. A quantitative and qualitative analysis of degeneration in the ventral root, including evidence for axon outgrowth and limb innervation prior to cell death.
    J Comp Neurol. 1978 Jan 1;177(1):59-85 PMID: 72762
  45. Retrograde axonal transport of locally synthesized proteins, e.g., actin and heat shock protein 70, in regenerating adult frog sciatic sensory axons.
    J Neurosci Res. 1994 Jul 1;38(4):424-32 PMID: 7523692
  46. Neuron death in vertebrate development: in vitro methods.
    Methods Cell Biol. 1995;46:277-321 PMID: 7609654
  47. Peptide inhibitors of the ICE protease family arrest programmed cell death of motoneurons in vivo and in vitro.
    Neuron. 1995 Aug;15(2):385-93 PMID: 7646891
  48. Differential distribution of 70-kD heat shock protein in atherosclerosis. Its potential role in arterial SMC survival.
    Arterioscler Thromb Vasc Biol. 1995 Jan;15(1):27-36 PMID: 7749813
  49. Motoneurons deprived of trophic support in vitro require new gene expression to undergo programmed cell death.
    J Neurobiol. 1994 Aug;25(8):1005-16 PMID: 7964701
  50. Inhibition of ischaemic tolerance in the gerbil hippocampus by quercetin and anti-heat shock protein-70 antibody.
    Neuroreport. 1993 Jun;4(6):695-8 PMID: 8347809
  51. The constitutive and stress inducible forms of hsp 70 exhibit functional similarities and interact with one another in an ATP-dependent fashion.
    J Cell Biol. 1993 Mar;120(5):1101-12 PMID: 8436586
  52. Molecular chaperones in cellular protein folding.
    Nature. 1996 Jun 13;381(6583):571-9 PMID: 8637592
  53. Cell stress genes and neuronal protection.
    Neuropathol Appl Neurobiol. 1995 Dec;21(6):475-7 PMID: 8745232
  54. Neurotrophic survival molecules for motoneurons: an embarrassment of riches.
    Neuron. 1996 Aug;17(2):195-7 PMID: 8780643
  55. Role of neurotrophic factors in neuronal development.
    Curr Opin Neurobiol. 1996 Feb;6(1):64-70 PMID: 8794045
  56. Toxicity and tolerability of recombinant human ciliary neurotrophic factor in patients with amyotrophic lateral sclerosis.
    Neurology. 1996 Nov;47(5):1329-31 PMID: 8909453
  57. Cooperative action of Hsp70, Hsp90, and DnaJ proteins in protein renaturation.
    Biochemistry. 1996 Nov 26;35(47):14889-98 PMID: 8942653
  58. Hsp70 prevents activation of stress kinases. A novel pathway of cellular thermotolerance.
    J Biol Chem. 1997 Jul 18;272(29):18033-7 PMID: 9218432
  59. A hitchhiker's guide to the human Hsp70 family.
    Cell Stress Chaperones. 1996 Apr;1(1):23-8 PMID: 9222585
  60. Exogenous heat shock cognate protein Hsc 70 prevents axotomy-induced death of spinal sensory neurons.
    Cell Stress Chaperones. 1996 Sep;1(3):161-6 PMID: 9222601
  61. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis.
    Mol Cell Biol. 1997 Sep;17(9):5317-27 PMID: 9271409
  62. Effects of exogenous stress protein 70 on the functional properties of human promonocytes through binding to cell surface and internalization.
    Cell Stress Chaperones. 1998 Mar;3(1):67-77 PMID: 9585183
  63. Heat shock protein 72 modulates pathways of stress-induced apoptosis.
    J Biol Chem. 1998 Jul 3;273(27):17147-53 PMID: 9642282
  64. Heat shock and apoptosis. The two defense systems of the organism may have overlapping molecular elements.
    Ann N Y Acad Sci. 1998 Jun 30;851:67-74 PMID: 9668607
  65. Increased production of amyloid precursor protein provides a substrate for caspase-3 in dying motoneurons.
    J Neurosci. 1998 Aug 1;18(15):5869-80 PMID: 9671674
  66. A placebo-controlled trial of insulin-like growth factor-I in amyotrophic lateral sclerosis. European ALS/IGF-I Study Group.
    Neurology. 1998 Aug;51(2):583-6 PMID: 9710040
  67. A novel strategy for introducing exogenous bcl-2 into neuronal cells: the Cre/loxP system-mediated activation of bcl-2 for preventing programmed cell death using recombinant adenoviruses.
    Mol Cell Neurosci. 1998 Sep;12(1-2):65-78 PMID: 9770341
  68. Involvement of specific caspases in motoneuron cell death in vivo and in vitro following trophic factor deprivation.
    Mol Cell Neurosci. 1998 Oct;12(3):157-67 PMID: 9790736
  69. Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology.
    Pharmacol Ther. 1998 Nov;80(2):183-201 PMID: 9839771
  70. Heat shock proteins chaperoning life and death.
    Cell Stress Chaperones. 1998 Dec;3(4):221-7 PMID: 9880234
  71. Heat shock proteins: regulators of stress response and apoptosis.
    Cell Stress Chaperones. 1998 Dec;3(4):228-36 PMID: 9880235
  72. Intranuclear targeted delivery of functional NF-kappaB by 70 kDa heat shock protein.
    EMBO J. 1999 Jan 15;18(2):411-9 PMID: 9889197
Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.1912-05.2005
Published
2005-10-19
Pages
9735-45
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6725726
Subset
IM
Grants
Intramural NIH HHS · United States
NINDS NIH HHS · R01 NS046615 · United States
NINDS NIH HHS · NS03061 · United States
NINDS NIH HHS · NS046615 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.1912-05.2005 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2