In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance

Guzhova, Irina V.; Kislyakova, Ksenia; Moskaliova, Olesia; Fridlanskaya, Irina; Tytell, Michael; Cheetham, Michael E.; Margulis, Boris A.

doi:10.1016/s0006-8993(01)02774-3

Cited by 295 publications

(232 citation statements)

References 30 publications

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“…Consequently, transport [37,40] would require either increased cell membrane permeability [29] or a specific exocytotic pathway, as already was reported from a hepatosplanchnic source [28] and from the brain [45] following body exercise. A possible way of specific exocytotic transport via an alternative vesicular pathway not involving the endoplasmic reticulum-Golgi compartment was already reported [13].…”

Section: The Origin Of Salivary Chaperone Hsp70mentioning

confidence: 60%

“…By using ATP, and working in concert with other chaperones and co-chaperones, the members of the Hsp70-family take part in nearly all of the typical intracellular chaperone functions, including protein folding [21,22,30,38], refolding of damaged proteins [68], inhibition of aggregation [30,38], resolubilization of aggregated proteins [73], the transport of several proteins [30,38], and the control of several signal transduction pathways [9,60], including the induction of senescence [24]. Furthermore, Hsp70 proteins are also involved in many processes outside the cell, including cytoprotection [36,37,41], cytokine-releasing effects, and the modulation of various immune functions [39,51,53,54,64,65,72,76,84].…”

Section: Members Of the Hsp70 Molecular Chaperone Familymentioning

confidence: 99%

“…There is increasing evidence for functions of Hsp70 outside of the cell, such as cytoprotection [36,37,41] and modulation of cytokine release and immunity [39,51,53,54,58,63,65,72,76,84]. All these functions may be important in relation to salivary Hsp70.…”

Section: Introductionmentioning

confidence: 99%

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Potential immunological functions of salivary Hsp70 in mucosal and periodontal defense mechanisms

Fábían

Fejérdy

Nguyen

et al. 2007

Arch. Immunol. Ther. Exp.

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Molecular chaperones were considered to be intracellular, but there is increasing evidence demonstrating their cytoprotective and immune modulator properties outside the cell. The major extracellular chaperone (Hsp70) was also found in saliva, indicating a possible effect of Hsp70 on mucosal surfaces. Here we summarize the immune-modulatory role of the 70-kDa stress protein family, with special attention on the potential impact of salivary Hsp70 on oral defense mechanisms. There are three major facets of Hsp70-induced immune activation: 1) the appearance of Hsp70 on the surface of certain tumor cells or virally infected cells, leading to their phagocytosis and subsequent lysis; 2) the role of extracellular uncomplexed Hsp70 as a danger signal, leading to the secretion of proinflammatory cytokines from antigen-presenting cells and T lymphocytes and of nitric oxide from macrophages as well as to complement activation; 3) receptor-mediated uptake of peptide-loaded Hsp70 to antigen-presenting cells and cross-presentation of the Hsp70-peptide complex as an antigen to cytotoxic T cells and natural killer lymphocytes. The immune-activating effect of salivary Hsp70 may also be highly important in oral defense, especially in areas where molecular and cellular participants of the immune response appear on the surface of the oral cavity (i.e. several lesions of the mucosa and the periodontal tissues).

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Section: The Origin Of Salivary Chaperone Hsp70mentioning

confidence: 60%

Section: Members Of the Hsp70 Molecular Chaperone Familymentioning

confidence: 99%

See 1 more Smart Citation

Potential immunological functions of salivary Hsp70 in mucosal and periodontal defense mechanisms

Fábían

Fejérdy

Nguyen

et al. 2007

Arch. Immunol. Ther. Exp.

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“…Previous studies have shown the release of hsp's into the cultured media by rat and chick embryo cells, squid glial cells, and yeast following heat shock (Hightower and Guidon, 1989;Russo et al, 1992;Guzhova et al, 2001). It is believed that these hsp's are important in cell proliferation during embryo morphogenesis, in addition to acting as protective factors for the surrounding cells in the presence of environmental stress (Hightower and Guidon, 1989;Russo et al, 1992;Guzhova et al, 2001). Our extensive literature search indicates that this is the first time that the Hsp70 secretion is documented in mouse and human prostate cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Forced expression of heat-shock protein 70 increases the secretion of Hsp70 and provides protection against tumour growth

2004

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Although heat-shock protein 70 (Hsp70) has been considered an intracellular protein, we report that Hsp70 is secreted under normal cell culture conditions by human prostate cell lines, LAPC-4, PC-3, CWR-22, RWPE-1 and -2, LNCaP, and TRAMP (transgenic adenocarcinoma mouse prostate)-C2. We found that the secretion can be enhanced by transfection with cDNA encoding for Hsp70. To verify that the Hsp70 detected in the supernatant was not secondary to cell leakage, C2 cells were cotransfected with cytoplasmic Renilla luciferase as a reporter. High levels of activities were noted in the cell extracts, while no enzyme activities were detected in the supernatants. To verify that forced oversecretion of Hsp70 could protect against tumour growth, mice were injected with C2 cells transfected with an Hsp70 DNA construct and challenged with live tumour cells. Mice injected with cells transfected with the Hsp70 DNA construct demonstrated a significantly decreased rate of tumour growth compared to those injected with empty vector. In addition, a difference in survival rate as defined by a surrogate end point was noted between the two groups. In a second experiment, we developed a cell line that stably overexpressed Hsp70. Mice injected with these cells also demonstrated a significant decrease in tumour growth and significantly increased survival.

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“…The first evidence for this Hsp70 function was suggested in 1980s, when it was shown to transferred from glial cells to axons and to be released from cultured cells (Tytell et al 1986;Hightower and Guidon 1989). Recently it has been demonstrated that glial cells release Hsp70 making neurons, which are exposed to the protein more resistant to cell stress (Guzhova et al 2001;Tytell 2005). The A6 cells, a clone of mouse mesoangioblasts, synthesize the Hsp70 under physiological growth conditions and this synthesis is independent from HSF1 or HSF2, but its role is not yet defined (Geraci et al 2006).…”

Section: Introductionmentioning

confidence: 99%

Hsp70 localizes differently from chaperone Hsc70 in mouse mesoangioblasts under physiological growth conditions

et al. 2008

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Mouse A6 mesoangioblasts express Hsp70 even in the absence of cellular stress. Its expression and its intracellular localization were investigated under normal growth conditions and under hyperthermic stress. Immunofluorescence assays indicated that without any stress a fraction of Hsp70 co-localized with actin microfilaments, in the cell cortex and in the contractile ring of dividing cells, while the Hsc70 chaperone did not. Hsp70 immunoprecipitation assays confirmed that a portion of Hsp70 binds actin. Immunoblot assays showed that both proteins were present in the nucleus. After heat treatment Hsp70 and actin continued to co-localize in the leading edge of A6 cells but not on microfilaments. Although Hsp70 and Hsc70 are both basally synthesized they showed different cellular distribution, suggesting an Hsp70 different activity respect to the Hsc70 chaperone. Moreover, we found Hsp70 in the culture medium as it has been described in other cell types.

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In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance

Cited by 295 publications

References 30 publications

Potential immunological functions of salivary Hsp70 in mucosal and periodontal defense mechanisms

Potential immunological functions of salivary Hsp70 in mucosal and periodontal defense mechanisms

Forced expression of heat-shock protein 70 increases the secretion of Hsp70 and provides protection against tumour growth

Hsp70 localizes differently from chaperone Hsc70 in mouse mesoangioblasts under physiological growth conditions

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