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Estrogen deprivation does not affect vascular heat shock response in female rats: a comparison with oxidative stress markers

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Abstract

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.

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Abbreviations

HS:

Heat shock

HSP70:

The 70 kDa family of heat shock proteins

E2:

Estradiol

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Acknowledgments

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.

Ethical approval

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.

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Authors and Affiliations

  1. Laboratory of Cellular Physiology, Department of Physiology, Institute of Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite 500, ICBS, 2° andar, Porto Alegre, RS, 90050-170, Brazil

    Antônio Azambuja Miragem & Paulo Ivo Homem de Bittencourt Jr.

  2. Federal Institute of Education, Science and Technology “Farroupilha”, Santa Rosa, RS, Brazil

    Antônio Azambuja Miragem

  3. Department of Life Sciences, Regional University of the Northwest of Rio Grande do Sul State, Ijuí, RS, Brazil

    Mirna Stela Ludwig, Thiago Gomes Heck, Fernanda Giesel Baldissera, Analu Bender dos Santos & Matias Nunes Frizzo

  4. Postgraduate Program in Integral Attention to Health (PPGAIS-UNIJUI/UNICRUZ), Ijuí, RS, Brazil

    Mirna Stela Ludwig, Thiago Gomes Heck, Analu Bender dos Santos & Matias Nunes Frizzo

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  1. Antônio Azambuja Miragem
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  2. Mirna Stela Ludwig
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Correspondence to Paulo Ivo Homem de Bittencourt Jr..

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Miragem, A.A., Ludwig, M.S., Heck, T.G. et al. Estrogen deprivation does not affect vascular heat shock response in female rats: a comparison with oxidative stress markers. Mol Cell Biochem 407, 239–249 (2015). https://doi.org/10.1007/s11010-015-2472-5

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