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Glucocorticoids regulate metallothionein-1/2 expression in rat choroid plexus: effects on apoptosis

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Abstract

The choroid plexus (CP) participates in the synthesis, secretion and regulation of the cerebrospinal fluid, in the removal of its toxic compounds and in the regulation of the availability of essential metal ions to the brain. It expresses and secretes metallothioneins 1/2 (MT-1/2) which are key components in the maintenance of the central nervous system metal homeostasis and have anti-apoptotic properties, thereby protecting the brain. Glucocorticoids regulate MT-1/2 expression in several brain regions, but within the choroid plexuses (CPs) it remains unknown. Glucocorticoid levels increase in response to stress with implications in apoptosis. Further, CP expresses glucocorticoid (GR) and mineralocorticoid receptors (MR) turning it into likely glucocorticoid responsive structure. Data prompted us to study the regulation of MT-1/2 expression in response to glucocorticoids in the rat CP, and to investigate its implications in apoptosis. MT-1/2 protein and mRNA expression analysis showed that hydrocortisone up-regulates MT-1/2 expression in rat choroid plexus (RCP) cell line and in primary cultures of choroid plexus epithelial cells (CPEC) cultures via GR and MR. Also, incubation of RCP cells with hydrocortisone significantly diminished apoptosis, an effect eliminated by the addition of a MT-1/2 antibody. Moreover, induction of psychosocial stress, with concomitant rise of corticosterone levels, increased MT-1/2 expression in liver and in CP of male and female rats, with an exception observed in CP from males subjected to acute stress in which down-regulation in MT-1/2 expression occurred. Altogether, the results obtained demonstrated that stress/glucocorticoids regulate MT-1/2 expression in rat CP, with implications on apoptosis.

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Acknowledgments

The work was supported by a grant from Fundação para a Ciência e Tecnologia from Portugal, through a doctoral fellowship attributed to Martinho A. (SFRH/BD/32424/2006). The authors also like to thank to Dr. Filomena Silva, Dr. Vítor Gaspar and Dr Mafalda Fonseca for their expert assistance and helpful advices in flow cytometry experiments.

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  1. CICS-UBI—Health Sciences Research Centre, University of Beira Interior, Av. Infante D. Henrique, Covilhã, 6200-506, Portugal

    A. Martinho, I. Gonçalves & C. R. Santos

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  1. A. Martinho
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  2. I. Gonçalves
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Correspondence to C. R. Santos.

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Martinho, A., Gonçalves, I. & Santos, C.R. Glucocorticoids regulate metallothionein-1/2 expression in rat choroid plexus: effects on apoptosis. Mol Cell Biochem 376, 41–51 (2013). https://doi.org/10.1007/s11010-012-1547-9

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