Influence of heat shock on cell volume regulation: protection from hypertonic challenge in a human monocyte cell line

Oehler, Rudolf; Zellner, Maria; Hefel, Beate; Weingartmann, G.; Spittler, Andreas; Struse, Heidi M.; Roth, Erich

doi:10.1096/fasebj.12.7.553

Cited by 26 publications

(16 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Heat treatments are known to affect cell volume and pH regulation in isotonic as well as anisotonic conditions (27,29,30). Commonly observed responses to these treatments include a decrease in pH i and V cell as well as an augmented capacity to recover from an acid load and to maintain V cell under hypertonic conditions (adaptive response); this process by which cells subjected to shrinkage return to a normal volume has been called regulatory volume increase (4).…”

Section: Discussionmentioning

confidence: 99%

“…Commonly observed responses to these treatments include a decrease in pH i and V cell as well as an augmented capacity to recover from an acid load and to maintain V cell under hypertonic conditions (adaptive response); this process by which cells subjected to shrinkage return to a normal volume has been called regulatory volume increase (4). Whereas the Na ϩ /H ϩ and/or HCO 3 Ϫ /Cl Ϫ exchangers have been implicated in the adaptive responses (27,29,30), the role of various ion transport systems in the early heat-induced changes have received modest attention. Because inhibition of NKCC1 has been shown to decrease V cell under anisotonic conditions (49), the effect of a thermal stress on Na ϩ -K ϩ -Cl Ϫ cotransport could therefore contribute to the early morphological changes that are observed during changes in ambient temperatures.…”

Section: Discussionmentioning

confidence: 99%

“…However, PASK does not fit the usual profile of a scaffolding protein, exhibiting intrinsic kinase activity and sharing no homology with chaperones, cochaperones, or adaptor molecules. In this regard, hsp90 or calnexin would represent alternative candidates considering, moreover, that they have been implicated in a variety of ion transport processes (27)(28)(29)(30).…”

Section: Cation-clmentioning

confidence: 99%

See 2 more Smart Citations

Characterization of a Novel Interaction between the Secretory Na+-K+-Cl- Cotransporter and the Chaperone hsp90

Simard

Daigle

Bergeron

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

The first isoform of the Na ؉ -K ؉ -Cl ؊ cotransporter (NKCC1) is of central importance for the control of cellular ion concentration and epithelium-mediated salt secretion. Several studies have established that a change in intracellular [Cl ؊ ] (Cl ؊ i ) represents a key signaling mechanism by which NKCC1-induced Cl ؊ movement is autoregulated and by which Cl ؊ entry and exit on opposite sides of polarized cells are coordinated. Although this signaling mechanism is coupled to a pathway that leads to post-translational modification of the carrier, no unifying model currently accounts for the ion dependence of NKCC1 regulation. In this paper, evidence is presented for the first time that hsp90 associates with the cytosolic C terminus of NKCC1, probably when the carrier is predominantly in its unfolded form during early biogenesis. Evidence is also presented that the Cl ؊ i -dependent regulatory pathway can be activated by a thermal stress but that it is no longer operational if NKCC1-expressing cells are pretreated with geldanamycin, an antibiotic that inhibits hsp90, albeit nonspecifically. Taken together, our data indicate that binding of hsp90 to NKCC1 may be required for Na؊ cotransport to occur at the cell surface and that it could play an important role in ion-dependent signaling mechanisms, insofar as the maneuvers that were used to alter the expression or activity of the chaperone do not exert their main effect by inducing other cellular events such as the unfolded protein response. Further studies will be required to elucidate the functional relevance of this novel interaction. Cation-ClϪ cotransporters (CCCs) 1 are polytopic membrane proteins that couple the movement of Cl Ϫ to that of Na ϩ and/or K ϩ ions in or out of cells (1-4). Seven such proteins have been identified to date; the Na ϩ -K ϩ -Cl Ϫ cotransporters (NKCCs) isoform 1 and 2 (5, 6), the Na ϩ -Cl Ϫ cotransporter isoform 1 (7), and the K ϩ -Cl Ϫ cotransporters isoform 1-4 (8 -11). Other proteins that are homologous to the CCCs have also been identified (12); they are termed orphan CCCs because their ionic substrates have not been identified to date.The NKCC1 is considered a housekeeping carrier that is responsible for the bumetanide-sensitive component of Na ϩ -K ϩ -Cl Ϫ cotransport across cellular membranes (1-4). One of its main functions is to regulate cell volume (V cell ) and intracellular ClBecause of its basolateral localization in polarized cells, this carrier also promotes fluid and electrolyte secretion through a variety of epithelia by cooperating with apically disposed ion transport systems including Cl Ϫ channels (13-17). Several lines of evidence suggest that NKCC1 activity is increased by phosphorylation of its cytosolic termini (see Fig. 1) in response to Cl Ϫ i reduction or cell shrinkage. To this effect, recent studies have reported binding of proline-alanine-rich stress-related kinase (PASK) to NKCC1 and provided strong evidence that this interaction leads to phosphorylation-dependent activation of Na 18 -20). Along the sa...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Cation-clmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of a Novel Interaction between the Secretory Na+-K+-Cl- Cotransporter and the Chaperone hsp90

Simard

Daigle

Bergeron

et al. 2004

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Note that the eigenvalues are more or less uniformly distributed over approximately 6 orders of magnitude (with occasionally a few exceptionally sloppy eigenvectors); this behavior is characteristic of other sloppy systems (30)(31)(32)(33) …”

Section: Derivation Of Kinase Inactivation Inhibitory Mechanismmentioning

confidence: 88%

“…For example, what is the best p38 pathway target for blocking TNF-R 33 All proteins species are cytosolic, unless otherwise noted. b Initial condition fit to phospho-p38 data.…”

Section: Model Analysismentioning

confidence: 99%

Analysis of Mechanistic Pathway Models in Drug Discovery: p38 Pathway

2008

View full text Add to dashboard Cite

Mechanistic models of signal transduction have emerged as valuable tools for untangling complex signaling networks and gaining detailed insight into pathway dynamics. The natural extension of these tools is for the design of therapeutic strategies. We have generated a novel computational model of lipopolysaccharide-induced p38 signaling in the context of TNF-R production in inflammatory disease. Using experimental measurement of protein levels and phospho-protein time courses, populations of model parameters were estimated. With a collection of parameter sets, reflecting virtual diversity, we step through analysis of the p38 signaling pathway model to answer specific drug discovery questions regarding target prioritization, inhibitor simulation, model robustness and co-drugging. We demonstrate that target selection cannot be assessed independently from inhibitor mechanism of action and is also linked with robustness to cellular variability. Finally, we assert that in the face of parameter uncertainty one can still uncover consistent findings that can guide drug discovery efforts.

show abstract

Short‐term heat acclimation is effective and may be enhanced rather than impaired by dehydration

Garrett

Goosens

Rehrer

et al. 2014

American J Hum Biol

133

View full text Add to dashboard Cite

show abstract

Influence of heat shock on cell volume regulation: protection from hypertonic challenge in a human monocyte cell line

Cited by 26 publications

References 20 publications

Characterization of a Novel Interaction between the Secretory Na+-K+-Cl- Cotransporter and the Chaperone hsp90

Characterization of a Novel Interaction between the Secretory Na+-K+-Cl- Cotransporter and the Chaperone hsp90

Analysis of Mechanistic Pathway Models in Drug Discovery: p38 Pathway

Short‐term heat acclimation is effective and may be enhanced rather than impaired by dehydration

Contact Info

Product

Resources

About