Time and Tissue Dependent Expression of Heat Shock Protein 27, 70 and 90 in Mice Following Hyperthermia

Joshua Joseph Malago


Heat shock response is rapidly induced to protect cells from irreversible injury by stabilizing cellular synthetic and metabolic activities. Particularly, the response differentially protects against stresses, infections and inflammations. While it could be time- and tissue-dependent, it is not established as to how it exhibits. This study explored the expression of heat shock protein (Hsp) 27, 70 and 90 in intestines, kidneys, livers and lungs of mice undergoing hyperthermia at 42°C for 1 hr and recovering for 1-72 hr. The expression of these Hsps was determined by immunohistochemical staining of formalin-fixed paraffin-embedded tissue sections. There was an increase in the expression of Hsp27, 70 and 90 that peaked at 6-12 hr and differentially declined at 48-72 hr. The peak expression was reached earlier in the lung and dropped sharply in the intestine while sustained for a longer time in the liver and kidney. At 72 hr only Hsp90 exhibited moderate expression in the lung and kidney. It is concluded that optimal expression of Hsps is time- and tissue- dependent and has narrow margin of peak expression in some tissues. This knowledge might contribute to designing therapeutic agents for curbing stresses, infections and inflammations that can be suppressed by Hsps.

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. M. Lewis, P.J. Helmsing, M. Ashburner, M. Lewis, P.J. Helmsing, M. Ashburner M. “Parallel changes in puffing activity and patterns of protein synthesis in salivary glands of Drosophila.” Proc. Natl. Acad. Sci. U S A., vol. 72 pp. 3604-3608, Sep. 1975.

. J.F. Koninkx. “Protein synthesis in salivary glands of Drosophila Hydei after experimental gene induction.” Biochem. J., vol. 158 pp. 623-628, Sep. 1976.

. H. Ovelgonne, M. Bitorina, R. van Wijk. “Stressors specific activation of heat stock genes in H35 rat hepatoma cells.” Toxicol. Appl. Pharmacol., vol. 135 pp. 100-109, Nov. 1995.

. J.J. Malago, J.F.J.G. Koninkx, F.E. van Dijk JE. “The heat shock response and cytoprotection of the intestinal epithelium.” Cell Stress Chaperone, vol. 7 pp. 191–199, Apr. 2002.

. C. Wu. “Heat shock transcription factors, structure and regulation.” Annu. Rev. Dev. Biol., vol. 11 pp. 441-469, 1995.

. J.H. Ovelgonne, J.F.J.G. Koninkx, A. Pusztai, S. Bardocz, W. Kok, S.W. Ewen, H.G. Hendriks, J.E. van Dijk. “Decreased levels of Heat shock proteins in gut epithelia cells after exposure to plant lectin.” Gut, vol. 46 pp. 679-687, May 2000.

. M.G. Santoro. “Heat shock factors and the control of the stress response.” Biochem. Pharmacol., vol. 59 pp. 55-63, Jan. 2000.

. J.J. Malago, J.F.J.G. Koninkx, P.C.J. Tooten, E. van Liere, J.E. van Dijk. “Anti-inflammatory properties of heat shock protein 70 and butyrate on Salmonella-induced interleukin-8 secretion in enterocyte-like Caco-2 cells”. Clin. Exp. Immun., vol. 141 pp. 62-71, Jul. 2005.

. V.L. Gabai, A.B. Meriin, J.A. Yaglom, Z.V. Volloch, M.Y. Sherman. “Role of heat shock proteins70 in regulation of stress JNK: implications on apoptosis and aging.” Biomed. Res., vol. 438 pp. 1-4, Oct. 1998.

. W. Neuhofer, M.L. Fraek, N. Ouyang, F.X. Beck. “Differential expression of heat shock protein 27 and 70 in renal papillary collecting duct and interstitial cells implications for urea resistance.” J. Physiol., vol. 564 pp. 715-722, May 2005.

. F. Burette, S. Pinah, S. Giunts, F. Vittone, J.M. Forbes, R. Chiarle, M. Arnstein, P.C. Perin, G. Camussi, M.E. Copper, G. Gruden. “Heat shock protein expression in diabetic nephropathy.” Am. J. Physiol. Renal Physiol., vol. 295 pp. 1817-1824, Dec. 2008.

. E. Najemnikova, C.D. Rodgers, M. Locke M. “Altered heat stress response following streptozotocin-induced diabetes.” Cell Stress Chaperones, vol. 12 pp. 342-352, Winter 2007.

. H. Ren, M.W. Musch, K. Kojima, D. Boone, A. Ma, E.B. Chang. “Short chain fatty acids induce intestinal epithelial heat shock protein 25 expression in rats and IEC 18 cell.” Gastroenterology, vol. 121 pp. 631-639, Sep. 2001.

. A. Stojadinovic, J. Kiang, J. Gold Hill, D. Martin, R. Smallridge, R. Galloway, T. Shea-Donohue. "Induction of heat shock response prevents tissue injury during acute inflammation of the rat ileum”. Crit. Care Med., vol. 25 pp. 309-317, Feb. 1997.

. S. Uchida, M. Fujiki, Y. Nagai, T. Abe, H. Kobayashi. “Geranylgeranylacetone a non invasive heat shock protein inducer, induces protein Kinase C and leads to neuroprotection against cerebral infarction in rats.” Neuro. Sci. Let., vol. 396 pp. 220-224, Apr. 2006.

. A. Lu, R.Q. Ran, J. Clark, M. Reilly, A. Nee, F.R. Sharp. “17-beta-Estradiol induces Heat shock protein in brain arteries and potentiates ischemic Hsp induction in glia and neurons.” J. Cereb. Blood Flow. Metab., vol. 22 pp. 183-195, Feb. 2002.

. S. Otan, M. Otaka, M. Jin, A. Okuyama, S. Hoh, A. Iwabuchi, H. Sasahara, H. Hoh, Y. Tashima, O. Masamune. “Effect of pre induction of heat shock protein on acetic acid-induced colitis in rats.” Dig. Dis. Sci., vol. 42 pp. 833-846, Apr. 1997.

. J.P. Simard, D.N. Reynolds, A.P. Kraguljac, G.S. Smith, D.D. Mosser. “Overexpression of HSP70 inhibits cofilin phosphorylation and promotes lymphocyte migration in heat-stressed cells.” J. Cell Sci., vol. 124(Pt 14) pp. 2367-2374, Jul. 2011.

. J.J. Malago JJ (2003). “The role of the heat shock response in the cytoprotection of the intestinal epithelium.” PhD, Utrecht University, Utrecht, The Netherlands, Oct. 2003.

. Y. Qin, Y. Naito, O. Handa, N. Hayashi, A. Kuki, K. Mizushima, T. Omatsu, Y. Tanimura, M. Morita, S. Adachi, A. Fukui, I. Hirata, E. Kishimoto, T. Nishikawa, K. Uchiyama, T. Ishikawa, T. Takagi, N. Yagi, S. Kokura, T. Yoshikawa. “Heat shock protein 70-dependent protective effect of polaprezinc on acetylsalicylic acid-induced apoptosis of rat intestinal epithelial cells.” J. Clin. Biochem. Nutr., vol. 49 pp. 174-181, Nov. 2011.

. J.R. Ostberg, K.C. Kaplan, E.A. Repasky. “Induction of stress proteins in a panel of mouse tissues by fever-range whole body hyperthermia.” Int. J. Hyperthermia, vol. 18 pp. 552-562, Nov.-Dec. 2002.

. H. Sareh, M.E. Tulapurkar, N.G. Shah, I.S. Singh, J.D. Hasday. “Response of mice to continuous 5-day passive hyperthermia resembles human heat acclimation.” Cell Stress Chaperones, vol. 16 pp. 297-307, May 2011.

. P. Manzerra, S.J. Rush, I.R. Brown. “Tissue-specific differences in heat shock protein Hsc70 and Hsp70 in the control and hyperthermic rabbit.” J. Cell Physiol., vol. 170 pp. 130-137, Feb. 1997.

. L. Huang, N.F. Mivechi, D. Moskophidis. “Insights into regulation and function of the major stress-induced hsp70 molecular chaperone in vivo: analysis of mice with targeted gene disruption of the Hsp70.1 or Hsp70.3 gene”. Mol. Cell Biol., vol. 21 pp. 8575-8591, 2001.

. B. Gong, G.K. Asimakis, Z. Chen, T.B. Albrecht, P.J. Boor, T.C. Pappas, B. Bell, M. Motamedi. “Whole-body hyperthermia induces up-regulation of vascular endothelial growth factor accompanied by neovascularization in cardiac tissue”. Life Sci., 79:1781-1788, Oct. 2006.

. V. Tanwar, J. Sachdeva, M. Golecha, S. Kumari, D.S. Arya DS. “Curcumin protects rat myocardium against isoproterenol–induced ischemic injury: attenuation of ventricular dysfunction through increased expression of Hsp27 along with strengthening antioxidant defense system.” J. Cardiovasc. Pharmacol., vol. 55 pp. 377-384, Apr. 2010.

. N. Fujio, T. Hatayama, H. Kinoshita, M. Yauikoka. “Inductions of mRNAs for heat shock proteins of rats after ischemia and partial hepatectomy.” Mol. Cell Biochem., vol. 77 pp. 173-177, Oct. 1987.

. Y. Cheng, Y. Liu, J. Liang. “Zinc is a potent Hsp inducer during liver cold preservation in rats.” Chin. Med. J. (Engl), vol. 115 pp. 1777-1779, Dec. 2002.

. D.L. Arvans, S.R. Vavricka, H. Ren, M.W. Musch, L. Kand, F.G. Rocha, A. Lucioni, J.R. Turner, J. Alverdy, E.B. Chang. “Luminal bacterial flora determines physiological expression of intestinal epithelial cytoprotective heat shock proteins 25 and 27.” Am. J. Physiol. Gastrointest. Liver Physiol., vol. 288 pp. 696-704, Apr. 2005.

. H.M. Sidahmed, N.M. Hashim, S. Mohan, S.I. Abdelwahab, M.M. Taha, F. Dehghan, M. Yahayu, G.C. Ee, M.F. Loke, J. Vadivelu. “Evidence of the gastroprotective and anti-Helicobacter pylori activities of β-mangostin isolated from Cratoxylum arborescens (vahl) blume.” Drug Des Devel Ther., vol. 10 pp. 297-313, Jan. 2016.

. A. Gupta, Z.A. Cooper, M.E. Tulapurkar, R. Potla, T. Maity, J.D. Hasday, I.S. Singh. “Toll-like receptor agonists and febrile range hyperthermia synergize to induce heat shock protein 70 expression and extracellular release.” J. Biol. Chem., vol. 288 pp. 2756-2766, Jan. 2013.

. F. Wei, H. Wang, J. Zhang, X. Chen, C. Li, Q. Huang. “Pharmacokinetics of combined gene therapy expressing constitutive human GM-CSF and hyperthermia-regulated human IL-12”. J. Exp. Clin. Cancer Res., vol. 32 pp. 5, Jan. 2013.

. S.K. Calderwood, J.R. Theriault, J. Gong. “How is the immune response affected by hyperthermia and heat shock proteins?” Int. J. Hyperthermia, vol. 21 pp. 713-716, Dec. 2005.


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