title: Aging-associated changes in oxidative stress, cell proliferation, and apoptosis are prevented in the prostate of transgenic rats overexpressing regucalcin.
abstract: Regucalcin (RGN) is a calcium (Ca(2+))-binding protein that displays a characteristic downregulated expression with aging in several tissues. Besides its role in regulating intracellular Ca(2+) 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.
authors.affiliation: CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Cátia V
authors.initials: CV
authors.lastname: Vaz
authors.affiliation: CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Marques
authors.affiliation: CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Cláudio J
authors.initials: CJ
authors.lastname: Maia
authors.affiliation: CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal. Electronic address: ssocorro@fcsaude.ubi.pt.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Socorro
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002265:Carboxylic Ester Hydrolases; D049109:Cell Proliferation; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D018384:Oxidative Stress; D011467:Prostate / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic
chemical_list: D002135:Calcium-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D002265:Carboxylic Ester Hydrolases; C513325:Rgn protein, rat