{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T02:36:35Z","timestamp":1772850995030,"version":"3.50.1"},"reference-count":34,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2012,10,15]]},"abstract":"<jats:p>Expression of GSK-3\u03b1 is increased in aging hearts and those subjected to hemodynamic overload. Overexpressed GSK-3\u03b1 inhibits ERK and enhances pressure overload (PO)-induced cardiac dysfunction. We studied whether suppression of the MEK1\/ERK pathway contributes to cardiac responses induced by overexpressed GSK-3\u03b1 using constitutively active MEK1 (CA-MEK1)\/GSK-3\u03b1 bigenic mice (bigenic mice), which were obtained by crossing cardiac-specific GSK-3\u03b1 transgenic mice (Tg-GSK) and cardiac-specific CA-MEK1 transgenic mice (Tg-MEK1). The suppression of ERK phosphorylation observed in Tg-GSK was eliminated in bigenic mice. At 12 mo, left ventricular (LV) weight\/tibia length, LV weight\/body weight, and cardiac myocyte size were significantly smaller in Tg-GSK than in nontransgenic mice (NTg), but were not significantly different between Tg-MEK1 and bigenic mice. The LV ejection fraction (LVEF), fractional shortening (FS), and change in pressure over time were significantly lower in Tg-GSK than in NTg, but were not significantly different between bigenic mice and Tg-MEK1. The increase in apoptosis in Tg-GSK was abolished in bigenic mice, although the increase in fibrosis was not. After PO, the decrease in cardiac hypertrophy and the enhancement of apoptosis seen in Tg-GSK were abrogated in bigenic mice. After PO, the LVEF and FS were significantly reduced in Tg-GSK compared with its sham, but not in NTg, Tg-MEK1, or bigenic mice compared with their respective shams. There was no significant difference in LVEF and FS between bigenic mice and Tg-MEK1 after PO. In conclusion, inhibition of the MEK1\/ERK pathway mediates the hypertrophy suppression and cardiac dysfunction caused by GSK-3\u03b1 overexpression in cardiac myocytes.<\/jats:p>","DOI":"10.1152\/ajpheart.00415.2012","type":"journal-article","created":{"date-parts":[[2012,8,18]],"date-time":"2012-08-18T05:31:02Z","timestamp":1345267862000},"page":"H979-H988","source":"Crossref","is-referenced-by-count":21,"title":["Constitutively active MEK1 rescues cardiac dysfunction caused by overexpressed GSK-3\u03b1 during aging and hemodynamic pressure overload"],"prefix":"10.1152","volume":"303","author":[{"given":"Yasuhiro","family":"Maejima","sequence":"first","affiliation":[{"name":"Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry, New Jersey, New Jersey Medical School, Newark, New Jersey; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan","family":"Galeotti","sequence":"additional","affiliation":[{"name":"Cardiovascular Research Institute, Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry, New Jersey, New Jersey Medical School, Newark, New Jersey; 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