Abstract
Heat shock proteins (Hsp) are ubiquitously expressed proteins, which are highly inducible by a variety of stressful stimuli. As organisms age, various denatured proteins such as proteins modified by oxidation have been detected. Such abnormal proteins might serve as stress signals for the induction of Hsp, which plays indispensable roles in protecting proteins from denaturation. Although it is well known that the heat shock induced expression of Hsp decreases with age, little attention has been given to the unstimulated, basal levels of Hsp. Therefore, a study was performed to examine the expression pattern of various Hsp with aging, under normal physiological conditions in human peripheral blood cells. The basal levels of Hsp32, Hsp70 and Hsp90 increased significantly with age in controls but not patients. Moreover, the levels of Hsp32, Hsp70, Hsp90, but not Hsp27 correlated positively among each other, indicating both common and different regulatory mechanisms. Higher levels of Hsp32, Hsp70 and Hsp90 were noticed in patients with inflammation, a commonly occurring natural stimulant of Hsp production, compared to control subjects. The production of Hsp appeared to be related to the circulating levels of C-reactive protein and cytokines.
Similar content being viewed by others
Abbreviations
- HS:
-
Heat shock
- HSF:
-
Heat shock factor
- Hsp:
-
Heat shock protein(s)
- MFI:
-
Mean fluorescence intensity
- PBMC:
-
Peripheral blood mononuclear cells
- ROS:
-
Reactive oxygen species
References
Ananthan J, Goldberg AL, Voellmy R (1986) Abnormal proteins serve as eukaryotic stress signals and trigger the activation of heat shock genes. Science 232(4749):522–524
Bajramovic JJ, Bsibsi M, Geutskens SB et al (2000) Differential expression of stress proteins in human adult astrocytes in response to cytokines. J Neuroimmunol 106(1–2):14–22
Bandres E, Merino J, Vazquez B et al (2000) The increase of IFN-gamma production through aging correlates with the expanded CD8(+high)CD28(−)CD57(+) subpopulation. Clin Immunol 96(3):230–235
Beresford PJ, Jaju M, Friedman RS et al (1998) A role for heat shock protein 27 in CTL-mediated cell death. J Immunol 161(1):161–167
Berlett BS, Stadtman ER (1997) Protein oxidation in aging, disease, and oxidative stress. J Biol Chem 272(33):20313–20316
Blake MJ, Fargnoli J, Gershon D et al (1991) Concomitant decline in heat-induced hyperthermia and HSP70 mRNA expression in aged rats. Am J Physiol 260(4 Pt 2):R663–R667
Bokov A, Chaudhuri A, Richardson A (2004) The role of oxidative damage and stress in aging. Mech Ageing Dev 125(10–11):811–826
Bruunsgaard H, Pedersen M, Pedersen BK (2001) Aging and proinflammatory cytokines. Curr Opin Hematol 8(3):131–136
Cabiscol E, Levine RL (1995) Carbonic anhydrase III. Oxidative modification in vivo and loss of phosphatase activity during aging. J Biol Chem 270(24):14742–14747
Charveron M, Calvo M, Gall Y (1995) Cell stress and implications of the heat-shock response in skin. Cell Biol Toxicol 11(3–4):161–165
Cornelussen RN, Gupta S, Knowlton AA (2001) Regulation of prostaglandin A1-induced heat shock protein expression in isolated cardiomyocytes. J Mol Cell Cardiol 33(8):1447–1454
De AK, Kodys KM, Yeh BS et al (2000) Exaggerated human monocyte IL-10 concomitant to minimal TNF-alpha induction by heat-shock protein 27 (Hsp27) suggests Hsp27 is primarily an antiinflammatory stimulus. J Immunol 165(7):3951–3958
Ensor JE, Wiener SM, McCrea KA et al (1994) Differential effects of hyperthermia on macrophage interleukin-6 and tumor necrosis factor-alpha expression. Am J Physiol 266(4 Pt 1):C967–C974
Ershler WB, Sun WH, Binkley N et al (1993) Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production is modifiable by dietary restriction. Lymphokine Cytokine Res 12(4):225–230
Feder ME, Hofmann GE (1999) Heat-shock proteins, molecular chaperones, and the stress response: evolutionary and ecological physiology. Annu Rev Physiol 61:243–282
Ferrucci L, Guralnik JM, Studenski S et al (2004) Designing randomized, controlled trials aimed at preventing or delaying functional decline and disability in frail, older persons: a consensus report. J Am Geriatr Soc 52(4):625–634
Frydman J, Nimmesgern E, Ohtsuka K et al (1994) Folding of nascent polypeptide chains in a high molecular mass assembly with molecular chaperones. Nature 370(6485):111–117
Goff SA, Goldberg AL (1985) Production of abnormal proteins in E. coli stimulates transcription of lon and other heat shock genes. Cell 41(2):587–595
Golden TR, Melov S (2001) Mitochondrial DNA mutations, oxidative stress, and aging. Mech Ageing Dev 122(14):1577–1589
Guo X, Shin VY, Cho CH (2001) Modulation of heme oxygenase in tissue injury and its implication in protection against gastrointestinal diseases. Life Sci 69(25–26):3113–3119
Hager K, Machein U, Krieger S et al (1994) Interleukin-6 and selected plasma proteins in healthy persons of different ages. Neurobiol Aging 15(6):771–772
Haire RN, Peterson MS, O’Leary JJ (1988) Mitogen activation induces the enhanced synthesis of two heat-shock proteins in human lymphocytes. J Cell Biol 106(3):883–891
Hamilton ML, Van Remmen H, Drake JA et al (2001) Does oxidative damage to DNA increase with age? Proc Natl Acad Sci USA 98(18):10469–10474
Hang H, He L, Fox MH (1995) Cell cycle variation of Hsp70 levels in HeLa cells at 37 degrees C and after a heat shock. J Cell Physiol 165(2):367–375
Hartl FU, Hlodan R, Langer T (1994) Molecular chaperones in protein folding: the art of avoiding sticky situations. Trends Biochem Sci 19(1):20–25
Heydari AR, Takahashi R, Gutsmann A et al (1994) Hsp70 and aging. Experientia 50(11–12):1092–1098
Hirose W, Ikematsu K, Tsuda R (2003) Age-associated increases in heme oxygenase-1 and ferritin immunoreactivity in the autopsied brain. Leg Med (Tokyo) 5(Suppl 1):S360–S366
Iijima N, Tamada Y, Hayashi S et al (1999) Expanded expression of heme oxygenase-1 (HO-1) in the hypothalamic median eminence of aged as compared with young rats: an immunocytochemical study. Neurosci Lett 271(2):113–116
Jaattela M (1999a) Escaping cell death: survival proteins in cancer. Exp Cell Res 248(1):30–43
Jaattela M (1999b) Heat shock proteins as cellular lifeguards. Ann Med 31(4):261–271
Jolly C, Morimoto RI (2000) Role of the heat shock response and molecular chaperones in oncogenesis and cell death. J Natl Cancer Inst 92(19):1564–1572
Kiang JG, Tsokos GC (1998) Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology. Pharmacol Ther 80(2):183–201
King V, Tower J (1999) Aging-specific expression of Drosophila hsp22. Dev Biol 207(1):107–118
Lantow M, Lupke M, Frahm J et al (2006) ROS release and Hsp70 expression after exposure to 1,800 MHz radiofrequency electromagnetic fields in primary human monocytes and lymphocytes. Radiat Environ Biophys 45(1):55–62
Lavoie JN, Gingras-Breton G, Tanguay RM et al (1993) Induction of Chinese hamster HSP27 gene expression in mouse cells confers resistance to heat shock. HSP27 stabilization of the microfilament organization. J Biol Chem 268(5):3420–3429
Lavrovsky Y, Song CS, Chatterjee B et al (2000) Age-dependent increase of heme oxygenase-1 gene expression in the liver mediated by NFkappaB. Mech Ageing Dev 114(1):49–60
Lee TS, Tsai HL, Chau LY (2003) Induction of heme oxygenase-1 expression in murine macrophages is essential for the anti-inflammatory effect of low dose 15-deoxy-Delta 12,14-prostaglandin J2. J Biol Chem 278(21):19325–19330
Maiello M, Boeri D, Sampietro L et al (1998) Basal synthesis of heat shock protein 70 increases with age in rat kidneys. Gerontology 44(1):15–20
Malmberg KJ, Arulampalam V, Ichihara F et al (2001) Inhibition of activated/memory (CD45RO(+)) T cells by oxidative stress associated with block of NF-kappaB activation. J Immunol 167(5):2595–2601
Maly FE, Nakamura M, Gauchat JF et al (1989) Superoxide-dependent nitroblue tetrazolium reduction and expression of cytochrome b-245 components by human tonsillar B lymphocytes and B cell lines. J Immunol 142(4):1260–1267
Martin GR, Danner DB, Holbrook NJ (1993) Aging—causes and defenses. Annu Rev Med 44:419–429
Njemini R, Abeele MV, Demanet C et al (2002) Age-related decrease in the inducibility of heat-shock protein 70 in human peripheral blood mononuclear cells. J Clin Immunol 22(4):195–205
Njemini R, Lambert M, Demanet C et al (2005) Heat shock protein 32 in human peripheral blood mononuclear cells: effect of aging and inflammation. J Clin Immunol 25(5):405–417
Njemini R, Lambert M, Demanet C et al (2003) The induction of heat shock protein 70 in peripheral mononuclear blood cells in elderly patients: a role for inflammatory markers. Hum Immunol 64(6):575–585
Park KJ, Gaynor RB, Kwak YT (2003) Heat shock protein 27 association with the I kappa B kinase complex regulates tumor necrosis factor alpha-induced NF-kappa B activation. J Biol Chem 278(37):35272–35278
Pratt WB (1993) The role of heat shock proteins in regulating the function, folding, and trafficking of the glucocorticoid receptor. J Biol Chem 268(29):21455–21458
Sakata-Kaneko S, Wakatsuki Y, Matsunaga Y et al (2000) Altered Th1/Th2 commitment in human CD4 + T cells with ageing. Clin Exp Immunol 120(2):267–273
Sandmand M, Bruunsgaard H, Kemp K et al (2003) High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes. Gerontology 49(3):155–160
Siu PM, Pistilli EE, Alway SE (2005) Apoptotic responses to hindlimb suspension in gastrocnemius muscles from young adult and aged rats. Am J Physiol Regul Integr Comp Physiol 289(4):R1015–R1026
Stephanou A, Amin V, Isenberg DA et al (1997) Interleukin 6 activates heat-shock protein 90 beta gene expression. Biochem J 321( Pt 1):103–106
Stephanou A, Isenberg DA, Akira S et al (1998) The nuclear factor interleukin-6 (NF-IL6) and signal transducer and activator of transcription-3 (STAT-3) signalling pathways co-operate to mediate the activation of the hsp90beta gene by interleukin-6 but have opposite effects on its inducibility by heat shock. Biochem J 330( Pt 1):189–195
Stephanou A, Isenberg DA, Nakajima K et al (1999) Signal transducer and activator of transcription-1 and heat shock factor-1 interact and activate the transcription of the Hsp-70 and Hsp-90beta gene promoters. J Biol Chem 274(3):1723–1728
Stephanou A, Latchman DS (1999) Transcriptional regulation of the heat shock protein genes by STAT family transcription factors. Gene Expr 7(4–6):311–319
Tavaria M, Gabriele T, Kola I et al (1996) A hitchhiker’s guide to the human Hsp70 family. Cell Stress Chaperones 1(1):23–28
Tu N, Hu Y, Mivechi NF (2006) Heat shock transcription factor (Hsf)-4b recruits Brg1 during the G1 phase of the cell cycle and regulates the expression of heat shock proteins. J Cell Biochem 98(6):1528–1542
Unno K, Asakura H, Shibuya Y et al (2000) Increase in basal level of Hsp70, consisting chiefly of constitutively expressed Hsp70 (Hsc70) in aged rat brain. J Gerontol A Biol Sci Med Sci 55(7):B329–B335
Wheeler JC, Bieschke ET, Tower J (1995) Muscle-specific expression of Drosophila hsp70 in response to aging and oxidative stress. Proc Natl Acad Sci USA 92(22):10408–10412
Winfield JB (1989) Stress proteins, arthritis, and autoimmunity. Arthritis Rheum 32(12):1497–1504
Yokota S, Yokosawa N, Kubota T et al (2003) Suppression of thermotolerance in mumps virus-infected cells is caused by lack of HSP27 induction contributed by STAT-1. J Biol Chem 278(43):41654–41660
Zampetaki A, Minamino T, Mitsialis SA et al (2003) Effect of heme oxygenase-1 overexpression in two models of lung inflammation. Exp Biol Med (Maywood) 228(5):442–446
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Njemini, R., Lambert, M., Demanet, C. et al. Basal and infection-induced levels of heat shock proteins in human aging. Biogerontology 8, 353–364 (2007). https://doi.org/10.1007/s10522-006-9078-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10522-006-9078-y