Heat shock treatment protects osmotic stress–induced dysfunction of the blood-brain barrier through preservation of tight junction proteins

Lu, Tzongshi; Chen, Hsiang-Wen; Huang, Maw-Hsiung; Wang, Shu-Jung; Yang, Rei‐Cheng

doi:10.1379/csc-45r1.1

Cited by 25 publications

(24 citation statements)

References 38 publications

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“…9). Other reports support the finding that heat-shock proteins can interact with the TJ; in endothelial cells, an interaction between Hsp70 and ZO-1 has been reported (Lu et al, 2004), and another member of the Hsp70 family, Apg-2, binds to ZO-1, localizes in the TJ and co-precipitates after heat shock (Tsapara et al, 2006). Taken together, we speculate that ZO-1, Src, G␣12 and other components of the TJ complex are in close proximity and/or in Fig.…”

Section: Regulation Of Tight Junctionssupporting

confidence: 59%

Gα12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly

Sabath

Negoro

Beaudry

et al. 2008

Journal of Cell Science

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The polarized functions of epithelia require an intact tight junction (TJ) to restrict paracellular movement and to separate membrane proteins into specific domains. TJs contain scaffolding, integral membrane and signaling proteins, but the mechanisms that regulate TJs and their assembly are not well defined. Gα12 (GNA12) binds the TJ protein ZO-1 (TJP1), and Gα12 activates Src to increase paracellular permeability via unknown mechanisms. Herein, we identify Src as a component of the TJ and find that recruitment of Hsp90 to activated Gα12 is necessary for signaling. TJ integrity is disrupted by Gα12-stimulated Src phosphorylation of ZO-1 and ZO-2 (TJP2); this phosphorylation leads to dissociation of occludin and claudin 1 from the ZO-1 protein complex. Inhibiting Hsp90 with geldanamycin blocks Gα12-stimulated Src activation and phosphorylation, but does not affect protein levels or the Gα12–ZO-1 interaction. Using the calcium-switch model of TJ assembly and GST-TPR (GST-fused TPR domain of PP5) pull-downs of activated Gα12, we demonstrate that switching to normal calcium medium activates endogenous Gα12 during TJ assembly. Thrombin increases permeability and delays TJ assembly by activating Gα12, but not Gα13, signaling pathways. These findings reveal an important role for Gα12, Src and Hsp90 in regulating the TJ in established epithelia and during TJ assembly.

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Section: Regulation Of Tight Junctionssupporting

confidence: 59%

Gα12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly

Sabath

Negoro

Beaudry

et al. 2008

Journal of Cell Science

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“…If the former, perhaps the preservation of gastrointestinal barrier integrity is of greater clinical relevance for maintaining BBB integrity. From a molecular viewpoint, what is the role of heat shock proteins (e.g., HSP 72) in BBB permeability during heat stress (261,266,402)? Future studies employing known (S100B) and novel [e.g., matrix metalloproteinases (36)] transcerebral markers for BBB permeability in humans, is warranted.…”

Section: Bbb Permeabilitymentioning

confidence: 99%

Cerebral Vascular Control and Metabolism in Heat Stress

Bain

Nybo

Ainslie

2015

Comprehensive Physiology

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This review provides an in-depth update on the impact of heat stress on cerebrovascular functioning. The regulation of cerebral temperature, blood flow, and metabolism are discussed. We further provide an overview of vascular permeability, the neurocognitive changes, and the key clinical implications and pathologies known to confound cerebral functioning during hyperthermia. A reduction in cerebral blood flow (CBF), derived primarily from a respiratory-induced alkalosis, underscores the cerebrovascular changes to hyperthermia. Arterial pressures may also become compromised because of reduced peripheral resistance secondary to skin vasodilatation. Therefore, when hyperthermia is combined with conditions that increase cardiovascular strain, for example, orthostasis or dehydration, the inability to preserve cerebral perfusion pressure further reduces CBF. A reduced cerebral perfusion pressure is in turn the primary mechanism for impaired tolerance to orthostatic challenges. Any reduction in CBF attenuates the brain's convective heat loss, while the hyperthermic-induced increase in metabolic rate increases the cerebral heat gain. This paradoxical uncoupling of CBF to metabolism increases brain temperature, and potentiates a condition whereby cerebral oxygenation may be compromised. With levels of experimentally viable passive hyperthermia (up to 39.5-40.0 °C core temperature), the associated reduction in CBF (∼ 30%) and increase in cerebral metabolic demand (∼ 10%) is likely compensated by increases in cerebral oxygen extraction. However, severe increases in whole-body and brain temperature may increase blood-brain barrier permeability, potentially leading to cerebral vasogenic edema. The cerebrovascular challenges associated with hyperthermia are of paramount importance for populations with compromised thermoregulatory control--for example, spinal cord injury, elderly, and those with preexisting cardiovascular diseases.

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“…It is possible that the MIB pathway may be favored over the use of cotransporters in the brain because of lower BBB permeability towards myo-inositol relative to glucose (Pasquali et al, 2010). Interestingly, in mammals, an increase in general permeability of the BBB can be induced by hyperosmotic challenge (Lu et al, 2004;Mackie et al, 1986;Wilhelm et al, 2008). The likely mechanism for this effect is temporary cell shrinkage, which creates openings in the tight junctions between brain capillary endothelial cells (Davson and Segal, 1996).…”

Section: Selective Permeability Of Teleost Bbb Favors Mib Pathwaymentioning

confidence: 99%

Tilapia (Oreochromis mossambicus) brain cells respond to hyperosmotic challenge by inducingmyo-inositol biosynthesis

Gardell

Yang

Sacchi

et al. 2013

Journal of Experimental Biology

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SUMMARYThis study aimed to determine the regulation of the de novo myo-inositol biosynthetic (MIB) pathway in Mozambique tilapia (Oreochromis mossambicus) brain following acute (25 ppt) and chronic (30, 60 and 90 ppt) salinity acclimations. The MIB pathway plays an important role in accumulating the compatible osmolyte, myo-inositol, in cells in response to hyperosmotic challenge and consists of two enzymes, myo-inositol phosphate synthase and inositol monophosphatase. In tilapia brain, MIB enzyme transcriptional regulation was found to robustly increase in a time (acute acclimation) or dose (chronic acclimation) dependent manner. Blood plasma osmolality and Na + and Cl -concentrations were also measured and significantly increased in response to both acute and chronic salinity challenges. Interestingly, highly significant positive correlations were found between MIB enzyme mRNA and blood plasma osmolality in both acute and chronic salinity acclimations. Additionally, a mass spectrometry assay was established and used to quantify total myo-inositol concentration in tilapia brain, which closely mirrored the hyperosmotic MIB pathway induction. Thus, myo-inositol is a major compatible osmolyte that is accumulated in brain cells when exposed to acute and chronic hyperosmotic challenge. These data show that the MIB pathway is highly induced in response to environmental salinity challenge in tilapia brain and that this induction is likely prompted by increases in blood plasma osmolality. Because the MIB pathway uses glucose-6-phosphate as a substrate and large amounts of myo-inositol are being synthesized, our data also illustrate that the MIB pathway likely contributes to the high energetic demand posed by salinity challenge.

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Heat shock treatment protects osmotic stress–induced dysfunction of the blood-brain barrier through preservation of tight junction proteins

Cited by 25 publications

References 38 publications

Gα12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly

Gα12 regulates protein interactions within the MDCK cell tight junction and inhibits tight-junction assembly

Cerebral Vascular Control and Metabolism in Heat Stress

Tilapia (Oreochromis mossambicus) brain cells respond to hyperosmotic challenge by inducingmyo-inositol biosynthesis

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