Invited Symposium: SERCA-Type of Calcium Pumps and Phospholamban
Discussion and Conclusion
Our data indicate that SERCA 3b is ubiquitously expressed in tissues containing arterial endothelial cells (aorta, coronary vessels from heart), epithelial (trachea, intestine, thymus, lung, kidney) and lymphoid tissues (thymus, spleen) and that SERCA 3a is present in epithelial and lymphoid tissues but not in endothelial cells. In human, SERCA 3a and 3b were both detected in platelets and in a lymphoid cell line (Jurkat) whereas only SERCA 3a was present in the epithelial-like HeLa cell line . More recently, a third spliced mRNA population, SERCA 3c, was described in human and mouse tissues . Both in human and mouse tissues, when present, SERCA 3b and SERCA 3c are coexpressed with SERCA 3a which is the major isoform in all human tissues examined so far. The primers we used in figure 3B should detect SERCA 3c but we didn’t amplify it. Thus, if SERCA 3c is present at all, it must be at very low level. One cannot exclude that the 3b isoform we have seen in epithelial and lymphoid tissues correspond to endothelial cells of vessels. On the other hand, the presence of only SERCA 3a in HeLa cells may be due to a shift from expression of one isoform to the other during dedifferentiation of cells in culture as we have shown in smooth muscle cells for the SERCA 2 transcipts. To test the hypothesis that SERCA 3 has a particular role in endothelial cells and can regulate the vascular tone, G. Shull ‘s group has generated SERCA 3-deficient mice and analyzed contraction and relaxation of aortic rings and Ca2+ signaling in endothelial cells . Their results suggest that SERCA 3 plays an important role in mechanisms that mediate endothelium-dependent relaxation of vascular smooth muscle. Our data indicate that SERCA 3b is the only SERCA 3 isoform expressed in endothelial cells. Thus, SERCA 3b should be involved in synthesis or secretion of endothelial vasoactive peptides but a specific role for SERCA 3a remains to be elucidated. We have previously shown that SERCA 3 is expressed at early embryonic stages in the rat, especially in heart, dorsal aorta and liver . However, the knock-out data indicate that SERCA 3 is not absolutely necessary for development since the SERCA 3-deficient mice are viable and fertile. The role of SERCA3 in embryos is not yet known.
Vascular smooth muscle cells undergo a transition from a « contractile » to a « proliferative » phenotype when they proliferate and this is accompagnied by changes in the expression of the genes encoding the major contractile proteins [18 ,19 for review]. Changes in reactivity to pharmacological agents affecting Ca2+ release from internal stores have also been described [20 , 21]. We present here the evidence that RASMC lose their caffeine-, ryanodine-sensitive store during proliferation . This is associated with the down-regulated SERCA 2a isoform. Previous studies [22 , 23] have shown that proliferation of VSMCs induced by PDGF-BB is associated with an increase in the expression of SERCA 2a isoform. Thus PDGF-BB is not involved in the phenomenon described here. It should be interesting to determine which growth factors are implicated in the reorganization of the calcium pools during proliferation.
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|Lompré, A-M; Ozog, A; Vallot, O; (1998). Control of Expression of SERCA 2 and SERCA 3 Spliced Variants. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/wuytack/lompre0338/index.html|
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