Estrogen deprivation does not affect vascular heat shock response in female rats: a comparison with oxidative stress markers
- 221 Downloads
Hot flashes, which involve a tiny rise in core temperature, are the most common complaint of peri- and post-menopausal women, being tightly related to decrease in estrogen levels. On the other hand, estradiol (E2) induces the expression of HSP72, a member of the 70 kDa family of heat shock proteins (HSP70), which are cytoprotective, cardioprotective, and heat inducible. Since HSP70 expression is compromised in age-related inflammatory diseases, we argued whether the capacity of triggering a robust heat shock (HS) response would be still present after E2 withdrawal. Hence, we studied the effects of HS treatment (hot tub) in female Wistar rats subjected to bilateral ovariectomy (OVX) after a 7-day washout period. Twelve h after HS, the animals were killed and aortic arches were surgically excised for molecular analyses. The results were compared with oxidative stress markers in the plasma (superoxide dismutase, catalase, and lipoperoxidation) because HSP70 expression is also sensitive to redox regulation. Extracellular (plasma) to intracellular HSP70 ratio, an index of systemic inflammatory status, was also investigated. The results showed that HS response was preserved in OVX animals, as inferred from HSP70 expression (up to 40 % rise, p < 0.01) in the aortas, which was accompanied by no further alterations in oxidative stress, hematological parameters, and glycemic control either. This suggests that the lack of estrogen per se could not be solely ascribed as the unique source of low HSP70 expression as observed in long-term post-menopausal individuals. As a consequence, periodic evaluation of HSP70 status (iHSP70 vs. eHSP70) may be of clinical relevance because decreased HS response capacity is at the center of the onset of menopause-related dysfunctions.
KeywordsHeat shock proteins HSP70 Estrogen deprivation Menopause Stress response
The 70 kDa family of heat shock proteins
This work was partially supported by grants received from the Brazilian National Council for Scientific and Technological Development (CNPq) #563870/2010-9, 402626/2012-5, and 402364/2012-0 to PIHBJ. TGH was supported by grants from CNPq (382692/2011-0) and the State of Rio Grande Foundation for Research Support (FAPERGS, 002106-2551/13-5). AAM, MSL, TGH, and PIHBJ designed the study. AAM, MSL, and TGH completed all the experiments described in this manuscript. FGB performed HS treatments, glucose status monitoring experiments, and Western analyses. Oxidative stress studies were conducted by ABS. MNF was involved in hematology and ELISA analyses. All authors were involved in analyzing the results. PIHBJ provided experimental advice and wrote the paper. All the authors had final approval of the submitted and published versions.
The procedures described herein were approved by the Federal University of Rio Grande do Sul Ethics Committee on Animal Experimentation (CEUA #19858), according to the guidelines of the Brazilian National Council for the Control of Animal Experimentation (CONCEA).
Conflict of interest
The authors declare no conflict of interest and no competing interests such as consultancies, financial involvement, and patent ownership in relation to the work described.
- 9.Ludwig MS, Minguetti-Câmara VC, Heck TG, Scomazzon SP, Nunes PR, Bazotte RB, Homem de Bittencourt PI Jr (2014) Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats: an effect associated with increased IL-6 levels but not with IL-10 or TNFα. Mol Cell Biochem 397:97–107. doi: 10.1007/s11010-014-2176-2 CrossRefPubMedGoogle Scholar
- 20.Knapp RT, Wong MJ, Kollmannsberger LK, Gassen NC, Kretzschmar A, Zschocke J, Hafner K, Young JC, Rein T (2014) Hsp70 cochaperones HspBP1 and BAG-1 M differentially regulate steroid hormone receptor function. PLoS One 9:e85415. doi: 10.1371/journal.pone.0085415 PubMedCentralCrossRefPubMedGoogle Scholar
- 23.Chung J, Nguyen AK, Henstridge DC, Holmes AG, Chan MH, Mesa JL, Lancaster GI, Southgate RJ, Bruce CR, Duffy SJ, Horvath I, Mestril R, Watt MJ, Hooper PL, Kingwell BA, Vigh L, Hevener A, Febbraio MA (2008) HSP72 protects against obesity-induced insulin resistance. Proc Natl Acad Sci USA 105:1739–1744. doi: 10.1073/pnas.0705799105 PubMedCentralCrossRefPubMedGoogle Scholar
- 25.Saha JK, Xia J, Grondin JM, Engle SK, Jakubowski JA (2005) Acute hyperglycemia induced by ketamine/xylazine anesthesia in rats: mechanisms and implications for preclinical models. Exp Biol Med (Maywood) 230:777–784Google Scholar
- 27.Febbraio MA, Mesa JL, Chung J, Steensberg A, Keller C, Nielsen HB, Krustrup P, Ott P, Secher NH, Pedersen BK (2004) Glucose ingestion attenuates the exercise-induced increase in circulating heat shock protein 72 and heat shock protein 60 in humans. Cell Stress Chaperon 9:390–396CrossRefGoogle Scholar
- 29.Homem de Bittencourt PI Jr, Lagranha DJ, Maslinkiewicz A, Senna SM, Tavares AMV, Baldissera P, Janner DR, Peralta JS, Bock PM, Gutierrez LLP, Scola G, Heck TG, Krause MS, Cruz LA, Abdalla DSP, Lima T, Curi R (2007) LipoCardium: endothelium-directed cyclopentenone prostaglandin-based liposome formulation that completely reverses atherosclerotic lesions. Atherosclerosis 193:245–258. doi: 10.16/j.atherosclerosis.2006.08.049 CrossRefPubMedGoogle Scholar
- 34.Kolberg A, Rosa TG, Puhl MT, Scola G, da Rocha Janner D, Maslinkiewicz A, Lagranha DJ, Heck TG, Curi R, de Bittencourt PI Jr (2006) Low expression of MRP1/GS-X pump ATPase in lymphocytes of Walker 256 tumour-bearing rats is associated with cyclopentenone prostaglandin accumulation and cancer immunodeficiency. Cell Biochem Funct 24:23–39. doi: 10.1002/cbf.1290 CrossRefPubMedGoogle Scholar
- 35.Krause MS, Heck TG, Bittencourt A, Scomazzon SP, Newsholme P, Curi R, Homem de Bittencourt PI Jr (2015) The chaperone balance hypothesis: the importance of the Extracellular to Intracellular HSP70 Ratio (eHSP70/iHSP70) to inflammation-driven type 2 Diabetes, the effect of exercise and the implications for clinical management. Mediat Inflamm 2015:249205. doi: 10.1155/2015/249205 CrossRefGoogle Scholar
- 45.Di Naso FC, Porto RR, Fillmann HS, Maggioni L, Padoin AV, Ramos RJ, Mottin CC, Bittencourt A, Marroni NA, Homem de Bittencourt PI Jr (2015) Obesity depresses the anti-inflammatory HSP70 pathway, contributing to NAFLD progression. Obesity 23:120–129. doi: 10.1002/oby.20919 CrossRefPubMedGoogle Scholar