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Differential translocation of heat shock factor-1 after mild and severe stress to human skin fibroblasts undergoing aging in vitro

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Repeated exposure to mild heat shock (HS) has been shown to induce a wide range of health promoting hormetic effects in various biological systems, including human cells undergoing aging in vitro. In order to understand how cells distinguish between mild and severe stress, we have investigated the extent of early and immediate HS response by analyzing the nuclear translocation of the transcription factor heat shock factor-1 (HSF1), in serially passaged normal adult human facial skin fibroblasts exposed to mild (41 °C) or severe (43 °C) HS. Cells respond differently when exposed to mild and severe HS at different passage levels in terms of the extent of HSF1 translocation. In early passage young cells there was a 5-fold difference between mild and severe HS in the extent of HSF1 translocation. However, in near senescent late passage cells, the difference between mild and severe stress in terms of the extent of HSF1 translocation was reduced to less than 2-fold. One of the reasons for this age-related attenuation of heat shock response is due to the fact there was a higher basal level of HSF1 in the nuclei of late passage cells, which is indicative of increased intrinsic stress during cellular aging. These observations are consistent with previously reported data that whereas repeated mild stress given at younger ages can slow down aging and increase the lifespan, the same level of stress given at older ages may not provide the same benefits. Therefore, elucidating the early and immediate steps in the induction of stress response can be useful in deciding whether a particular level of stress is potentially hormetically beneficial or not.

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References

  • Anckar J, Sistonen L (2011) Regulation of HSF1 function in the heat stress response: implications in aging and disease. Annu Rev Biochem 80:1089–1115

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA (2001) U-shaped dose-responses in biology, toxicology, and public health. Annu Rev Public Health 22:15–33

    Article  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Bachmann KA, Bailer AJ et al (2007) Biological stress response terminology: integrating the concepts of adaptive response and preconditioning stress within a hormetic dose–response framework. Toxicol Appl Pharmacol 222:122–128

    Article  CAS  PubMed  Google Scholar 

  • Ciocca DR, Arrigo AP, Calderwood SK (2013) Heat shock proteins and heat shock factor 1 in carcinogenesis and tumor development: an update. Arch Toxicol 87(1):19–48

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dimri GP, Lee X, Basile G et al (1995) A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci U S A 92:9363–9367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fonager J, Beedholm R, Clark BFC et al (2002) Mild stress-induced stimulation of heat shock protein synthesis and improved functional ability of human fibroblasts undergoing aging in vitro. Exp Gerontol 37:1223–1238

    Article  CAS  PubMed  Google Scholar 

  • Gayda M, Paillard F, Sosner P et al (2012) Effects of sauna alone and postexercise sauna baths on blood pressure and hemodynamic variables in patients with untreated hypertension. J Clin Hypertens 14:553–560

    Article  CAS  Google Scholar 

  • Gutsmann-Conrad A, Heydari AR, You S et al (1998) The expression of heat shock protein 70 decreases with cellular senescence in vitro and in cells derived from young and old human subjects. Exp Cell Res 241:404–413

    Article  CAS  PubMed  Google Scholar 

  • Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid strains. Exp Cell Res 25:585–621

    Article  CAS  PubMed  Google Scholar 

  • Hercus MJ, Loeschcke V, Rattan SIS (2003) Lifespan extension of Drosophila melanogaster through hormesis by repeated mild heat stress. Biogerontology 4:149–156

    Article  CAS  PubMed  Google Scholar 

  • Heydari AR, You S, Takahashi R et al (2000) Age-related alterations in the activation of heat shock transcription factor 1 in rat heapatocytes. Exp Cell Res 256:83–93

    Article  CAS  PubMed  Google Scholar 

  • Jørgensen P, Milkovic L, Zarkovic N, Waeg G, Rattan SIS (2014) Lipid peroxidation-derived 4-hydroxynonenal-modified proteins accumulate in human facial skin fibroblasts during ageing in vitro. Biogerontology 15:105–110

    Article  PubMed  Google Scholar 

  • Kraft DC, Deocaris CC, Rattan SIS (2006) Proteasomal oscillation during mild heat shock in aging human skin fibroblasts. Ann NY Acad Sci 1067:224–227

    Article  CAS  PubMed  Google Scholar 

  • Kukkonen-Harjula K, Kauppinen K (2006) Health effects and risks of sauna bathing. Int J circumpolar health 65:195–205

    Article  PubMed  Google Scholar 

  • Le Bourg E (2005) Hormetic protection of Drosophila melanogaster middle-aged male flie from heat stress by mildly stressing them at young age. Naturwissenchaften 92:293–296

    Article  CAS  Google Scholar 

  • Le Bourg E, Rattan SIS (eds) (2008) Mild stress and healthy aging: applying hormesis in aging research and interventions. Springer, Dordrecht

    Google Scholar 

  • Morley JF, Morimoto RI (2004) Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones. Mol Biol Cell 15:657–664

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nielsen ER, Eskildsen-Helmond Y, Rattan SIS (2006) MAP-kinases and heat shock-induced hormesis in human fibroblasts during serial passaging in vitro. Ann NY Acad Sci 1067:343–348

    Article  CAS  PubMed  Google Scholar 

  • Nørgaard R, Kassem M, Rattan SIS (2006) Heat shock-induced enhancement of osteoblastic differentiation of hTERT-immortlized mesenchymal stem cells. Ann NY Acad Sci 1067:443–447

    Article  PubMed  Google Scholar 

  • Norry FM, Loeschcke V (2002) Temperature-induced shifts in associations of longevity with body size in Drosophila melanogster. Evolution 56:299–306

    Article  PubMed  Google Scholar 

  • Olsen A, Vantipalli MC, Lithgow GJ (2006) Lifespan extension of Caenorhabditis elegans following repeated mild hormetic heat treatments. Biogerontology 7:221–230

    Article  PubMed  Google Scholar 

  • Paglin S, Lee NY, Nakar C et al (2005) Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 cells. Cancer Res 65:11061–11070

    Article  CAS  PubMed  Google Scholar 

  • Putics A, Végh EM, Csermely P et al (2008) Resveratrol induces the heat-shock response and protects human cells from severe heat stress. Antiox Red Sign 10:1–11

    Article  Google Scholar 

  • Rattan SIS (1998) Repeated mild heat shock delays ageing in cultured human skin fibroblasts. Biochem Mol Biol Int 45:753–759

    CAS  PubMed  Google Scholar 

  • Rattan SIS (2004) Hormetic mechanisms of anti-aging and rejuvenating effects of repeated mild heat stress on human fibroblasts in vitro. Rejuven Res 7:40–48

    Article  Google Scholar 

  • Rattan SIS (2008) Hormetic modulation of aging in human cells. In: Le Bourg E, Rattan SIS (eds) Mild stress and healthy aging: applying hormesis in aging research and interventions. Springer, Dordrecht, pp 81–96

    Chapter  Google Scholar 

  • Rattan SIS (2012) Cell Senescence In Vitro. In: eLS. John Wiley & Sons, Ltd. doi:10.1002/9780470015902.a0002567.pub3

  • Rattan SIS, Le Bourg E (eds) (2014) Hormesis in health and disease. CRC Press, Boca Raton

    Google Scholar 

  • Rattan SIS, Fernandes RA, Demirovic D (2009) Heat stress and hormetin-induced hormesis in human cells: effects on aging, wound healing, angiogenesis and differentiation. Dose-Response 7:93–103

    Article  Google Scholar 

  • Richter K, Haslbeck M, Buchner J (2010) The heat shock response: life on the verge of death. Mol Cell 40:253–266

    Article  CAS  PubMed  Google Scholar 

  • Scapagnini G, Davinelli S, Fortunati NA (2014) Thermal hydrotherapy as adaptive stress response: hormetic significance, mechanisms, and therapeutic implications. In: hormesis in health and disease. CRC Press, Boca raton, pp 151–164

    Google Scholar 

  • Soti C, Csermely P (2007) Aging cellular networks: chaperones as major participants. Exp Gerontol 42:113–119

    Article  CAS  PubMed  Google Scholar 

  • Verbeke P, Clark BFC, Rattan SIS (2001a) Reduced levels of oxidized and glycoxidized proteins in human fibroblasts exposed to repeated mild heat shock during serial passaging in vitro. Free Rad Biol Med 31:1593–1602

    Article  CAS  PubMed  Google Scholar 

  • Verbeke P, Fonager J, Clark BFC et al (2001b) Heat shock response and ageing: mechanisms and applications. Cell Biol Int 25:845–857

    Article  CAS  PubMed  Google Scholar 

  • Westerheide SD, Raynes R, Powell C et al (2012) HSF transcription factor family, heat shock response, and protein intrinsic disorder. Curr Protein and Pept Sci 13:86–103

    Article  CAS  Google Scholar 

  • Yates FE (1994) Order and complexity in dynamical systems: homeodynamics as a generalized mechanics for biology. Math Comput Model 19:49–74

    Article  Google Scholar 

Download references

Acknowledgments

Laboratory of Cellular Ageing is partially supported by a research grant from LVMH, France. The experimental work reported in this study was a part of the Ph.D. and M.Sc. research projects of the first two authors, DD and IMdT, respectively.

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Correspondence to Suresh I. S. Rattan.

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Demirovic, D., de Toda, I.M., Nizard, C. et al. Differential translocation of heat shock factor-1 after mild and severe stress to human skin fibroblasts undergoing aging in vitro . J. Cell Commun. Signal. 8, 333–339 (2014). https://doi.org/10.1007/s12079-014-0244-8

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  • DOI: https://doi.org/10.1007/s12079-014-0244-8

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