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I.R.F. / Aging news / General / 11092801

Transmembrane Protein Expression is Increasing with Age
Posted on: September 28, 2011

P-glycoprotein (P-gp) is a transmembrane protein that mediates the efflux of innumerous structurally unrelated compounds. It was initially found over-expressed in tumor cells, associated to a multidrug resistance phenotype (MDR). Then, P-gp was found constitutively expressed in excretory cells/tissues and in circulating cells, such as lymphocytes.

Considering the importance of this transporter in the establishment of therapeutic protocols and the existence of contradictory results, scientific study aimed at evaluating the influence of aging in the expression and function of P-gp in human lymphocytes, comparing two different methodologies to assess both parameters.

P-gp activity and expression were evaluated in lymphocytes isolated from whole blood samples of 65 healthy caucasian male donors, divided into two groups according to age (group 1: under 30-years old; group 2: above 60-years old). P-gp expression was assessed using the anti-P-gp monoclonal antibody, UIC2, in the presence and in absence of vinblastine (Vbl). P-gp activity was evaluated measuring the efflux rate of the fluorescent P-gp substrate rhodamine 123 (Rho 123) and also using UIC2 shift assay. Flow cytometric analysis was performed to assess all the proceedings. Furthermore, P-gp expression and each of the P-gp activity determination methods were compared, through correlation analysis and linear regression models.

Scientists observed a significant age-dependent increase in mean P-gp expression (p = 0.029), which was not reflected in the transporter's activity (p > 0.050).

Such result could be very interesting from another point of view. This is possible that not only P-gp expression shifts during aging process. This expression changes can be crucial if we will keep in mind growth factor receptor expression shifts, what can cause overconsumption of growth factors from blood, because of multiplied receptors on cells. This can cause the elimination of normal factor pool from blood to keep all vital function's proper work and it is possible that such kind of membrane protein expression increase can be one of the mechanisms to trigger aging onset.

Source: Vilas-Boas V, Silva R, Gaio AR, Martins AM, Lima SC, Cordeiro-da-Silva A, de Lourdes Bastos M, Remião F.; P-glycoprotein activity in human caucasian male lymphocytes does not follow its increased expression during aging.; Cytometry A. 2011 Sep 8. doi: 10.1002/cyto.a.21135. [Epub ahead of print]
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