Species-specific splicing and expression of angiotensin converting enzyme.
Angiotensin converting enzyme (ACE) is a critical determinant in the pathogenesis of various cardiovascular diseases and in the control of male fertility. Multiple isoforms of ACE protein are present in body fluids and tissues, but their formation and functions in vivo remain to be investigated. To determine whether alternative splicing contributes to the formation of ACE isoforms, this study was designed to clone all possible spliced transcripts in rat. We found that the splicing of intron 13 in testicular ACE was species-dependent. Compared with human and mouse testicular ACE, rat testicular ACE (rtACE) retained intron 13 in its mature transcripts. The insertion of the intron 13 did not change or shift the reading frame. Cloning and characterization of the rtACE showed that, in addition to testicular tissue, it was wildly expressed in somatic tissues, such as lung, kidney, cardiac ventricle, and skeletal muscle from both genders. Furthermore, we demonstrated that the expression of rtACE was developmentally up-regulated in testicular tissue and increased during cardiac hypertrophy. Our data suggests that the inclusion of intron 13 produces a novel ACE isoform. This isoform likely participates in local angiotensin II formation in both somatic and germinal tissues, and associates with certain physiological or pathophysiological events.
Tian
Xiao-Li
XL
Department of Toxicology, Institute of Clinical Pharmacology, Benjamin Franklin Medical Center, Free University of Berlin, Gary-Str. 5, D-14195 Berlin, Germany. tianx@ccf.org
Paul
Martin
M
D000595:Amino Acid Sequence; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D003001:Cloning, Molecular; D007438:Introns; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism; D014018:Tissue Distribution
D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A