Regucalcin (RGN) is a calcium (Ca2+)-binding protein that displays a characteristic downregulated expression with aging
in several tissues. Besides its role in regulating intracellular Ca2+ homeostasis, RGN has been associated with the control of oxidative stress, cell proliferation,
and apoptosis. Thus, the diminished expression of RGN with aging may contribute to
the age-associated deterioration of cell function. In the present study, we hypothesized
that the maintenance of high expression levels of RGN may prevent age-related alterations
in the processes mentioned previously. First, we confirmed that RGN expression is
significantly diminished in the prostate of 8-, 9-, 12-, and 24-months wild-type rats.
Then, the effect of aging on lipid peroxidation, antioxidant defenses, cell proliferation,
and apoptosis in the prostate of wild-type controls and transgenic rats overexpressing
RGN (Tg-RGN) was investigated. The activity of glutathione and the antioxidant capacity
were increased in Tg-RGN rats in response to the age-associated increase in thiobarbituric
acid reactive substances levels, an effect not seen in wild type. Overexpression of
RGN also counteracted the effect of aging increasing prostate cell proliferation.
In contrast to wild-type animals, the prostate weight of Tg-RGN did not change with
aging and was underpinned by the diminished expression of stem cell factor and c-kit,
and increased expression of p53. In addition, aged Tg-RGN animals displayed increased
expression (activity) of apoptosis regulators, therefore not showing the age-induced
resistance to apoptosis observed in wild type. Altogether, these findings indicate
the protective role of RGN against the development of age-related pathologies, such
as, for example, prostate cancer.
Abbreviations:
ABTS (2,2′-azino-di-[3-ethylbenzthiazoline sulfonate]), Ca2+ (calcium), CypA (cyclophylin A), FasL (Fas ligand), FasR (Fas receptor), GAPDH (glyceraldehyde 3-phosphate dehydrogenase), GST (glutathione S-transferase), MDA (malondialdehyde), pNA (p-nitroaniline), qPCR (Real-time PCR), RGN (regucalcin), ROS (reactive oxygen species), SCF (stem cell factor), SOD (superoxide dismutase), TAC (total antioxidant capacity), TBA (thiobarbituric acid), TBARS (thiobarbituric acid reactive substances), Tg-RGN (transgenic rats overexpressing RGN), WB (western blot)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: September 03, 2015
Accepted:
August 28,
2015
Received in revised form:
August 27,
2015
Received:
June 1,
2015
Identification
Copyright
© 2015 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
