Exogenous heat shock cognate protein Hsc70 prevents axotomy-induced death of spinal sensory neurons

Houenou, Lucien J.; Li, Linxi; Lei, Ming; Kent, Carol R.; Tytell, Michael

doi:10.1379/1466-1268(1996)001<0161:ehscph>2.3.co;2

Cited by 57 publications

(42 citation statements)

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“…Sciatic nerves were severed in postnatal day 5 (P5) BalB/ cByJ mice as described previously (Houenou et al 1996). Mice were anesthetized by hypothermia induced by contact with an ice-cold surface for approximately 2 minutes.…”

Section: Axotomymentioning

confidence: 99%

“…Sensory neuron survival was determined by neuronal cell counts in every fifth section of the L4 DRG. Only neurons with a large nucleus containing at least 1 distinct nucleolus and well-stained cytoplasm were counted, as previously described (Li et al 1994;Houenou et al 1996). Digital images of these tissue sections were obtained using a spot camera (Diagnostic Instruments) attached to a Zeiss Axioplan microscope.…”

Section: Neuronal Survival Determinationmentioning

confidence: 99%

“…Similarly, 25 g of rbHsp70 alone provided no MN survival-promoting effect (Fig 6). Sensory neuron survival was also examined after axotomy because it has been shown to be significantly improved by treatment using 5 g or more of a preparation of bovine brain Hsc70 that consisted of about 95% Hsc70 (Houenou et al 1996). Although the loss of DRG neurons after axotomy in the group that received saline or BSA was about half that of MNs, being 19.7% rather than 38.5%, certain doses of some of the Hsp preparations did significantly improve survival.…”

Section: Exogenous Application Of Hsps and Neuronal Survivalmentioning

confidence: 99%

“…Mature lumbar MNs do not undergo cell death after axotomy, whereas many MNs are still dependent on trophic support in the neonate, resulting in apoptosis and the loss of approximately 50% of the MNs after axotomy of the SN (Li et al 1994;Li et al 1998). Similarly, there is a loss of 30-35% of sensory neurons in the lumbar dorsal root ganglia (DRG) after sciatic axotomy in the neonate (Houenou et al 1996;Snider et al 1992).…”

Section: Introductionmentioning

confidence: 99%

“…In neural tissues, there are 4 reports substantiating the protective activity of exogenous Hsc/Hsp70. Work from this laboratory showed that an Hsc/Hsp70 mixture administered to the cut end of the SN or injected intravitreally into the rat eye prevented apoptotic cell death of sensory neurons or protected light-damaged photoreceptors from degeneration, respectively (Houenou et al 1996;Yu et al 2001). Guzhova et al (2001) documented that cultured glioma cells released Hsp70 and that a mixture of Hsc70 and Hsp70 was taken up by cultured neuroblastoma cells, rendering them resistant to apoptosis.…”

Section: Introductionmentioning

confidence: 99%

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Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration

Tidwell¹,

Houenou²,

Tytell³

2004

Cell Stress Chaper

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The induction of heat shock proteins (Hsps) serves not only as a marker for cellular stress but also as a promoter of cell survival, which is especially important in the nervous system. We examined the regulation of the constitutive and stress-induced 70-kD Hsps (Hsc70 and Hsp70, respectively) after sciatic nerve (SN) axotomy in the neonatal mouse. Additionally, the prevention of axotomy-induced SN cell death by administration of several preparations of exogenous Hsc70 and Hsp70 was tested. Immunohistochemistry and Western blot analyses showed that endogenous levels of Hsc70 and Hsp70 did not increase significantly in lumbar motor neurons or dorsal root ganglion sensory neurons up to 24 hours after axotomy. When a variety of Hsc70 and Hsp70 preparations at doses ranging from 5 to 75 g were applied to the SN stump after axotomy, the survival of both motor and sensory neurons was significantly improved. Thus, it appears that motor and sensory neurons in the neonatal mouse do not initiate a typical Hsp70 response after traumatic injury and that administration of exogenous Hsc/Hsp70 can remedy that deficit and reduce the subsequent loss of neurons by apoptosis.

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Section: Axotomymentioning

confidence: 99%

Section: Neuronal Survival Determinationmentioning

confidence: 99%

Section: Exogenous Application Of Hsps and Neuronal Survivalmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration

Tidwell¹,

Houenou²,

Tytell³

2004

Cell Stress Chaper

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Heat-shock proteins in axoplasm: High constitutive levels and transfer of inducible isoforms from glia

et al. 1998

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To characterize heat-shock proteins (HSPs) of the 70-kDa family in the crayfish medial giant axon (MGA), we analyzed axoplasmic proteins separately from proteins of the glial sheath. Several different molecular weight isoforms of constitutive HSP 70s that were detected on immunoblots were approximately 1-3% of the total protein in the axoplasm of MGAs. To investigate inducible HSPs, MGAs were heat shocked in vitro or in vivo, then the axon was bathed in radiolabeled amino acid for 4 hours. After either heat-shock treatment, protein synthesis in the glial sheath was decreased compared with that of control axons, and newly synthesized proteins of 72 kDa, 84 kDa, and 87 kDa appeared in both the axoplasm and the sheath. Because these radiolabeled proteins were present in MGAs only after heat-shock treatments, we interpreted the newly synthesized proteins of 72 kDa, 84 kDa, and 87 kDa to be inducible HSPs. Furthermore, the 72-kDa radiolabeled band in heat-shocked axoplasm and glial sheath samples comigrated with a band possessing HSP 70 immunoreactivity. The amount of heat-induced proteins in axoplasm samples was greater after a 2-hour heat shock than after a 1-hour heat shock. These data indicate that MGA axoplasm contains relatively high levels of constitutive HSP 70s and that, after heat shock, MGA axoplasm obtains inducible HSPs of 72 kDa, 84 kDa, and 87 kDa from the glial sheath. These constitutive and inducible HSPs may help MGAs maintain essential structures and functions following acute heat shock.

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Regulation of heat shock protein 70 release in astrocytes: Role of signaling kinases

Taylor

Robinson

Gifondorwa

et al. 2007

Developmental Neurobiology

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227

155

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The ability to mount a successful stress response in the face of injury is critical to the long-term viability of individual cells and to the organism in general. The stress response, characterized in part by the upregulation of heat shock proteins, is compromised in several neurodegenerative disorders and in some neuronal populations, including motoneurons (MNs). Because astrocytes have a greater capacity than neurons to survive metabolic stress, and because they are intimately associated with the regulation of neuronal function, it is important to understand their stress response, so that we may to better appreciate the impact of stress on neuronal viability during injury or disease. We show that astrocytes subjected to hyperthermia upregulate Hsp/c70 in addition to intracellular signaling components including activated forms of extracellular-signal-regulated kinase (ERK1/2), Akt, and c-jun N-terminal kinase/stress activated protein kinase (JNK/SAPK). Furthermore, astrocytes release increasing amounts of Hsp/c70 into the extracellular environment following stress, an event that is abrogated when signaling through the ERK1/2 and phosphatidylinositol-3 kinase (PI3K) pathways is compromised and enhanced by inhibition of the JNK pathway. Last, we show that the Hsp/c70 is released from astrocytes in exosomes. Together, these data illustrate the diverse regulation of stress-induced Hsp/c70 release in exosomes, and the way in which the balance of activated signal transduction pathways affects this release. These data highlight how stressful insults can alter the microenvironment of an astrocyte, which may ultimately have implications for the survival of neighboring neurons.

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Exogenous heat shock cognate protein Hsc70 prevents axotomy-induced death of spinal sensory neurons

Cited by 57 publications

References 0 publications

Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration

Administration of Hsp70 in vivo inhibits motor and sensory neuron degeneration

Heat-shock proteins in axoplasm: High constitutive levels and transfer of inducible isoforms from glia

Regulation of heat shock protein 70 release in astrocytes: Role of signaling kinases

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