Switch from actin alpha1 to alpha2 expression and upregulation of biomarkers for pressure overload and cardiac hypertrophy in taurine-deficient mouse heart.
Taurine is the most abundant free amino acid in heart muscle and protects against heart failure. In the present study, the consequences of hereditary taurine deficiency on cardiac gene expression were examined in 2- and 15-16-month-old taurine transporter knockout (taut(-/-)) mice using a mouse-specific DNA microarray. This oligonucleotide-based microarray contains probes for 251 genes with relevance for heart function. Of these, 163 probes exhibited a reproducible hybridization signal and were analyzed. alpha-Actin type 1 mRNA levels were 70% lower in the heart of young and older taut(-/-) mice compared to wild-type controls. Interestingly, the hearts of taut(-/-) mice showed a switch from alpha-actin 1 to alpha-actin 2 expression, as confirmed by real-time PCR and Western blot analysis. In addition, mRNA levels of biomarkers for pressure overload and hypertension were upregulated in taut(-/-) hearts, i.e., atrial natriuretic factor (+848%), brain natriuretic peptide (+90%), cardiac ankyrin repeat protein (+118%), and procollagen 1a1, 1a2 and 3a1 (+40% at least). These results point to a stress situation in the heart of taut(-/-) mice under laboratory conditions, and it can be speculated that taut(-/-) hearts may be even more susceptible to failure in the wild when under exogenous stress.
Warskulat
Ulrich
U
Klinik für Gastroenterologie, Hepatologie and Infektiologie, Heinrich-Heine-Universität Düsseldorf, D-40225 Düsseldorf, Germany. warskulat@med.uni-duesseldorf.de
Andrée
Birgit
B
Lüsebrink
Jessica
J
Köhrer
Karl
K
Häussinger
Dieter
D
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D001794:Blood Pressure; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007536:Isomerism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics; D013654:Taurine / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D000199:Actins; D015415:Biomarkers; D012333:RNA, Messenger; D013654:Taurine