Other
13 Authors
- Zhao A,
- Shioi T,
- Li C,
- McMullen JR,
- Williams DL,
- Browder IW,
- Kao RL,
- Ha T,
- Izumo S,
- Li Y,
- Haddad GE,
- Gao X,
- Kelley JL
| First Author | Ha T | Year | 2005 |
| Journal | Free Radic Biol Med | Volume | 39 |
| Issue | 12 | Pages | 1570-80 |
| PubMed ID | 16298682 | Mgi Jnum | J:104013 |
| Mgi Id | MGI:3611019 | Doi | 10.1016/j.freeradbiomed.2005.08.002 |
| Citation | Ha T, et al. (2005) Attenuation of cardiac hypertrophy by inhibiting both mTOR and NFkappaB activation in vivo. Free Radic Biol Med 39(12):1570-80 |
| abstractText | A role for the PI3K/Akt/mTOR pathway in cardiac hypertrophy has been well documented. We reported that NFkappaB activation is needed for cardiac hypertrophy in vivo. To investigate whether both NFkappaB activation and PI3K/Akt/mTOR signaling participate in the development of cardiac hypertrophy, two models of cardiac hypertrophy, namely, induction in caAkt-transgenic mice and by aortic banding in mice, were employed. Rapamycin (2 mg/kg/daily), an inhibitor of the mammalian target of rapamycin, and the antioxidant pyrrolidine dithiocarbamate (PDTC; 120 mg/kg/daily), which can inhibit NFkappaB activation, were administered to caAkt mice at 8 weeks of age for 2 weeks. Both rapamycin and PDTC were also administered to the mice immediately after aortic banding for 2 weeks. Administration of either rapamycin or PDTC separately or together to caAkt mice reduced the ratio of heart weight/body weight by 21.54, 32.68, and 42.07% compared with untreated caAkt mice. PDTC administration significantly reduced cardiac NFkappaB activation by 46.67% and rapamycin significantly decreased the levels of p70S6K by 34.20% compared with untreated caAkt mice. Similar results were observed in aortic-banding-induced cardiac hypertrophy in mice. Our results suggest that both NFkappaB activation and the PI3K/Akt signaling pathway participate in the development of cardiac hypertrophy in vivo. |
