(Hypertension. 2000;35:91.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Platelet Ca2+ATPases
A Plural, Species-Specific, and Multiple Hypertension-Regulated Expression System
From U 348 INSERM, IFR Circulation Lariboisière, Hôpital Lariboisière, Paris, France.
Correspondence to Virginie Martin, U 348 INSERM, IFR Circulation Lariboisière, Hôpital Lariboisière, 8 Rue Guy Patin, 75475 Paris, Cedex 10, France. E-mail jocelyne.enouf{at}inserm.lrb.ap-hop-paris.fr
Abstract—Gaining insight into nonmuscle Ca2+ signaling requires basic knowledge of the major structures involved. We investigated the expression of platelet Ca2+ATPases in normal and hypertension-associated abnormal Ca2+ signaling. First, overall identification of normotensive Wistar-Kyoto rat Ca2+ATPases was attempted by looking for newly described human platelet 3'-end alternatively spliced sarco/endoplasmic reticulum Ca2+ATPases (SERCA) 3b mRNA and plasma membrane Ca2+ATPase (PMCA) 1b and 4b proteins, in addition to SERCA2b and SERCA3a isoforms. For SERCAs, comparative analyses of human and Wistar-Kyoto rat SERCA3 platelet mRNA by reverse transcription–polymerase chain reaction (RT-PCR) followed by sequencing established that human platelets coexpressed SERCA3b and a third SERCA3c, while rat cells were devoid of them but expressed a still unknown splice variant that we termed rSERCA3b/3c. Its identification using 3'-end SERCA3 gene and rapid amplification of cDNA ends (RACE)–PCR studies showed that it results from an additional SERCA3 alternative splicing process, which uses a second alternative polyadenylation site located in the last intron. For PMCAs, with the use of gene-specific RT-PCR followed by sequencing and Western blotting using 5F10 monoclonal antibody, expression of human and rat platelet PMCA1b and PMCA4b was similar. Second, comparative analysis of these newly identified Ca2+ATPases and SERCA3a in age-matched spontaneously hypertensive rat platelets demonstrated (1) a marked downregulation of rSERCA3b/3c, which became null, and a 1.71-fold increase in SERCA3a and (2) an opposite regulation of the 2 PMCAs, namely, a 3.3-fold decrease in PMCA1b mRNA and a 3.7-fold increase in PMCA4b mRNA. Hence, platelets coexpress multiple, diverse, and species-specific Ca2+ATPases, including a novel fourth SERCA3. Moreover, expression of PMCA (1b and 4b), SERCA3a, and rSERCA3b/3c was modulated in rat hypertension. Hence, Ca2+ATPases should be regarded as constituting a new rational basis for the understanding of nonmuscle cell Ca2+ signaling.
Key Words: platelets • calcium • Ca2+ATPases • genes
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