RESUMO
BACKGROUND: Aging-related changes in important cellular pathways in the prostate may promote a permissive environment for an increased risk for prostatic disease development such as prostate cancer. Our objectives were to examine for such changes, by systematically determining the effects of growth and development and aging on proteomic profiles in different lobes of the rat prostate. METHODS: Prostate lobes (dorsolateral lobe, DL and ventral lobe, VL) were obtained from male Fisher rats of various ages representing young (4 months), mature (12 months), old (18 months), and very old (24 months). Differentially expressed proteins between age groups in each lobe were identified using a proteomic approach, isobaric Tags for Relative and Absolute Quantitation (iTRAQ). Select changes in the DL and VL were verified by immunoblot analysis. RESULTS: iTRAQ identified 317 proteins with high confidence. iTRAQ discovered 12 and 6 proteins significantly modulated in response to growth and development in the DL and VL, respectively, and 42 and 29 proteins significantly modulated in response to aging in the DL and VL, respectively. Proteins modulated during growth and development in the DL and VL are involved in a variety of biological processes including cell communication and development, whereas proteins modulated during aging were predominantly related to antioxidant activity and immunity. Immunoblot analysis verified age-related changes for α-1 antitrypsin, annexin A1, hypoxia up-regulated protein 1, and 78 kDa glucose-regulated protein. CONCLUSIONS: Aging results in changes in numerous prostatic proteins and pathways which are mainly linked to inflammation and may lead to prostatic disease development.
Assuntos
Envelhecimento/fisiologia , Longevidade/fisiologia , Próstata/crescimento & desenvolvimento , Proteômica/tendências , Transcriptoma/fisiologia , Animais , Masculino , Proteômica/métodos , Ratos , Ratos Endogâmicos F344RESUMO
Aging represents a major risk factor for prostate cancer; however, mechanisms responsible for this relationship remain unclear. Preclinical and some clinical investigations support the protective role of selenium against prostate cancer possibly through the reduction of oxidative stress. While increased levels of oxidative stress together with decreases in selenium and the major cellular antioxidant glutathione (GSH) are common in tissues of old animals, there is little data available on these parameters in the prostate. In the present study we have compared the levels of selenium, GSH and protein-bound GSH (GSSP) in blood and prostate tissues in young (4-month), mature (12-month), old (18 month), and very old (24 month) male F344 rats. Each prostate lobe (dorsolateral, DL; anterior, AL; ventral, VL) was analyzed separately based upon their differing potential for prostate cancer development. At all ages, selenium levels were lowest in DLAssuntos
Envelhecimento/metabolismo
, Glutationa/metabolismo
, Próstata/metabolismo
, Selênio/metabolismo
, Envelhecimento/sangue
, Envelhecimento/patologia
, Animais
, Peso Corporal/fisiologia
, Glutationa/sangue
, Masculino
, Tamanho do Órgão/fisiologia
, Próstata/anatomia & histologia
, Ratos
, Ratos Endogâmicos F344
, Selênio/sangue