{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T02:12:09Z","timestamp":1781835129556,"version":"3.54.5"},"reference-count":44,"publisher":"The Company of Biologists","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2007,2,1]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>The effect of physicochemical stress on organic anion transport across the vertebrate blood\u2013cerebrospinal fluid (CSF) barrier in the presence and absence of an endogenous cytoprotectant, trimethylamine oxide (TMAO), was investigated in isolated IVth choroid plexus (CP) of spiny dogfish shark(Squalus acanthias), an animal with naturally high levels of TMAO(\u223c70 mmol l\u20131). Active transepithelial absorption of the organic anion, 2,4-dichlorophenoxyacetic acid (2,4-D), by IVth CP mounted in Ussing chambers was measured after in vitro stress, and a marker for the cellular stress response, inducible heat shock protein 70 (Hsp70), was assayed by immunoblot analysis. Transient heat stress (a shift from the normal 13.5\u00b0C to 23.5\u00b0C for 1 h) decreased 2,4-D transport by \u223c66%;however, the same stress minus TMAO (isosmotic replacement with urea) had no effect on transport rate. In the absence of TMAO, stress-induced Hsp70 accumulation was more than double that seen in the presence of TMAO. Likewise,exposure to 50 \u03bcmol l\u20131 Zn for 6 h induced a twofold greater Hsp70 accumulation in the absence of TMAO than in its presence, and the higher Hsp70 level was associated with a higher 2,4-D transport rate. Heat stress and 50 \u03bcmol l\u20131 Zn also induced more pronounced increases in Hsp70 mRNA in the absence of TMAO. Thus, the cellular stress response can significantly alter CP organic anion transport capacity, and an endogenous osmolyte can suppress that response.<\/jats:p>","DOI":"10.1242\/jeb.02681","type":"journal-article","created":{"date-parts":[[2007,1,18]],"date-time":"2007-01-18T01:32:04Z","timestamp":1169083924000},"page":"541-552","source":"Crossref","is-referenced-by-count":39,"title":["Trimethylamine oxide suppresses stress-induced alteration of organic anion transport in choroid plexus"],"prefix":"10.1242","volume":"210","author":[{"given":"Alice R. A.","family":"Villalobos","sequence":"first","affiliation":[{"name":"Center for Membrane Toxicological Studies, Mount Desert Island Biological Laboratory, Salisbury Cove, ME 04672, USA"},{"name":"Environmental Medicine, University of Rochester, Rochester, NY 14642,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Larry","family":"Renfro","sequence":"additional","affiliation":[{"name":"Center for Membrane Toxicological Studies, Mount Desert Island Biological Laboratory, Salisbury Cove, ME 04672, USA"},{"name":"Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042500353868000_REF1","doi-asserted-by":"crossref","unstructured":"Agashe, V. R. and Hartl, F. U. (2000). Roles of molecular chaperones in cytoplasmic protein folding. Semin. Cell Dev. Biol.11,15-25.","DOI":"10.1006\/scdb.1999.0347"},{"key":"2021042500353868000_REF2","unstructured":"American Physiological Society (2002). Guiding principles for research involving animals and human beings. Am. J. Physiol.283,R281-R283."},{"key":"2021042500353868000_REF3","doi-asserted-by":"crossref","unstructured":"Ananthan, J., Goldberg, A. L. and Voellmy, R.(1986). Abnormal proteins serve as eukaryotic stress signals and trigger the activation of heat shock genes. Science232,522-524.","DOI":"10.1126\/science.3083508"},{"key":"2021042500353868000_REF4","doi-asserted-by":"crossref","unstructured":"Blake, M. J., Nowak, T. S. and Holbrook, N. J.(1990). In vivo hyperthermia induces expression of HSP70 mRNA in brain regions controlling the neuroendocrine response to stress. Brain Res. Mol. Brain. Res.8, 89-92.","DOI":"10.1016\/0169-328X(90)90014-5"},{"key":"2021042500353868000_REF5","doi-asserted-by":"crossref","unstructured":"Brown, C. R., Hong-Brown, L. Q., Biwersi, J., Verkman, A. S. and Welch, W. J. (1996). Chemical chaperones correct the mutant phenotype of the delta F508 cystic fibrosis transmembrane conductance regulator protein. Cell Stress Chaperones1, 117-125.","DOI":"10.1379\/1466-1268(1996)001<0117:CCCTMP>2.3.CO;2"},{"key":"2021042500353868000_REF6","doi-asserted-by":"crossref","unstructured":"Brown, C. R., Hong-Brown, L. Q. and Welch, W. J.(1997). Correcting temperature-sensitive protein folding defects. J. Clin. Invest.99,1432-1444.","DOI":"10.1172\/JCI119302"},{"key":"2021042500353868000_REF7","doi-asserted-by":"crossref","unstructured":"Brown, I. R. (1991). Expression of heat shock genes (hsp70) in the mammalian nervous system. In Results and Problems in Cell Differentiation: Heat Shock and Development. Vol. 17 (ed. L. E. Hightower and L. Nover), pp.215-229. New York: Springer-Verlag.","DOI":"10.1007\/978-3-540-46712-0_15"},{"key":"2021042500353868000_REF8","doi-asserted-by":"crossref","unstructured":"Brown, M. A., Upender, R. P., Hightower, L. E. and Renfro, J. L. (1992). Thermoprotection of a functional epithelium: heat stress effects on transepithelial transport by flounder renal tubule in primary monolayer culture. Proc. Natl. Acad. Sci. USA89,3246-3250.","DOI":"10.1073\/pnas.89.8.3246"},{"key":"2021042500353868000_REF9","doi-asserted-by":"crossref","unstructured":"Bukowski, J. A. and Lewis, R. J. (2000). Hormesis and health: a little of what you fancy may be good for you. South. Med. J.93,371-374.","DOI":"10.1097\/00007611-200093040-00004"},{"key":"2021042500353868000_REF10","doi-asserted-by":"crossref","unstructured":"Burg, M. B. and Peters, E. M. (1998). Effects of glycine betaine and glycerophosphocholine on thermal stability of ribonuclease. Am. J. Physiol.274,F762-F765.","DOI":"10.1152\/ajprenal.1998.274.4.F762"},{"key":"2021042500353868000_REF11","doi-asserted-by":"crossref","unstructured":"Calabrese, E. J. (2005). Paradigm lost,paradigm found: the re-emergence of hormesis as a fundamental dose response model in the toxicological sciences. Environ. Pollut.138,378-411.","DOI":"10.1016\/j.envpol.2004.10.001"},{"key":"2021042500353868000_REF12","doi-asserted-by":"crossref","unstructured":"Cousins, R. J., Liuzzi, J. P. and Lichten, L. A.(2006). Mammalian zinc transport, trafficking, and signals. J. Biol. Chem.281,24085-24089.","DOI":"10.1074\/jbc.R600011200"},{"key":"2021042500353868000_REF13","doi-asserted-by":"crossref","unstructured":"Ennis, S. R. and Keep, R. F. (2006). The effects of cerebral ischemia on the rat choroid plexus. J. Cereb. Blood Flow Metab.26,675-683.","DOI":"10.1038\/sj.jcbfm.9600224"},{"key":"2021042500353868000_REF14","doi-asserted-by":"crossref","unstructured":"Feder, J. H., Rossi, J. M., Solomon, J., Solomon, N. and Lindquist, S. (1992). The consequences of expressing hsp70 in Drosophila cells at normal temperatures. Genes Dev.6,1402-1413.","DOI":"10.1101\/gad.6.8.1402"},{"key":"2021042500353868000_REF15","doi-asserted-by":"crossref","unstructured":"Goldstein, L., Hartman, S. C. and Forster, R. P.(1967). On the origin of trimethylamine oxide in the spiny dogfish, Squalus acanthias.Comp. Biochem. Physiol.21,719-722.","DOI":"10.1016\/0010-406X(67)90467-7"},{"key":"2021042500353868000_REF16","doi-asserted-by":"crossref","unstructured":"Heads, R. J., Yellon, D. 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Hyperthermic induction of the 27-kDa heat shock protein (Hsp27) in neuroglia and neurons of the rat central nervous system. J. Comp. Neurol.428,495-510.","DOI":"10.1002\/1096-9861(20001218)428:3<495::AID-CNE7>3.0.CO;2-4"},{"key":"2021042500353868000_REF23","doi-asserted-by":"crossref","unstructured":"Kultz, D. (2005). Molecular and evolutionary basis of the cellular stress response. Annu. Rev. Physiol.67,225-257.","DOI":"10.1146\/annurev.physiol.67.040403.103635"},{"key":"2021042500353868000_REF24","doi-asserted-by":"crossref","unstructured":"Laity, J. H., Lee, B. M. and Wright, P. E.(2001). Zinc finger proteins: new insights into structural and functional diversity. Curr. Opin. Struct. Biol.11, 39-46.","DOI":"10.1016\/S0959-440X(00)00167-6"},{"key":"2021042500353868000_REF25","doi-asserted-by":"crossref","unstructured":"Liuzzi, J. P. and Cousins, R. J. (2004). Mammalian zinc transporters. Annu. Rev. 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(2004). Mechanisms of hormesis through mild heat stress on human cells. Ann. N. Y. Acad. Sci.1019,554-558.","DOI":"10.1196\/annals.1297.103"},{"key":"2021042500353868000_REF32","unstructured":"Renfro, J. L., Brown, M. A., Parker, S. L. and Hightower, L. E. (1993). Relationship of thermal and chemical tolerance to transepithelial transport by cultured flounder renal epithelium. J. Pharmacol. Exp. Ther.265,992-1000."},{"key":"2021042500353868000_REF33","doi-asserted-by":"crossref","unstructured":"Riabowol, K. T., Mizzen, L. A. and Welch, W. J.(1988). Heat shock is lethal to fibroblasts microinjected with antibodies against hsp70. Science242,433-436.","DOI":"10.1126\/science.3175665"},{"key":"2021042500353868000_REF34","doi-asserted-by":"crossref","unstructured":"Shabtay, A. and Arad, Z. (2005). Ectothermy and endothermy: evolutionary perspectives of thermoprotection by HSPs. J. Exp. 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