+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Rapamycin inhibits alpha 1-adrenergic receptor-stimulated cardiac myocyte hypertrophy but not activation of hypertrophy-associated genes. Evidence for involvement of p70 S6 kinase

, : Rapamycin inhibits alpha 1-adrenergic receptor-stimulated cardiac myocyte hypertrophy but not activation of hypertrophy-associated genes. Evidence for involvement of p70 S6 kinase. Circulation Research 81(2): 176-186

The 70-kD S6 kinase (p70S6K) has been implicated in the regulation of protein synthesis in many cell types and in the angiotensin II-stimulated hypertrophy of cardiac myocytes. Our purpose was to determine whether p70S6K plays a role in cardiomyocyte hypertrophy induced by the alpha 1-adrenergic receptor (alpha 1-AR) agonist phenylephrine (PE). PE stimulated the activity of p70S6K > 3-fold, and this increase was blocked by rapamycin, an immunosuppressant macrolide that selectively inhibits p70S6K. When administered for 3 days, PE stimulated a 30% increase in total protein content, a 2-fold increase in the incorporation of [14C]phenylalanine (14C-Phe) into protein, and a 50% increase in two-dimensional myocyte area. Rapamycin pretreatment (> or = 500 pg/mL) significantly inhibited each of these PE-stimulated changes. Two days of PE treatment resulted in a 1.6-fold increase in total RNA yield per dish, a 2-fold increase in incorporation of [14C]uridine into myocyte RNA, and increases in relative mRNA levels of the hypertrophy-associated atrial natriuretic factor (ANF, 2.1-fold) and skeletal alpha-actin (SK, 2.2-fold) genes. Although rapamycin abolished the PE-stimulated increases in total RNA and incorporation of [14C]uridine, it had no effect on the induction of the ANF and SK genes. LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-K) activity, inhibited PE-stimulated increases in p70S6K activity and the incorporation of labeled precursors into myocyte protein and RNA. These results demonstrate that p70S6K is activated by the hypertrophic agent PE and that a PI3-K or PI3-K-like activity is required for p70S6K activation and myocyte hypertrophy. The data suggest that p70S6K activation may be required for PE-stimulated hypertrophy of cardiac myocytes. Our results demonstrate that intracellular signaling pathways responsible for transcriptional and translational responses diverge early after alpha 1-AR stimulation in cardiac myocytes.


PMID: 9242178

Other references

Biswal, B.M.han; Lal, P.; Rath, G.K.shore; Shukla, N.K.mar; Mohanti, B.K.lyan; Deo, S., 1995: Intrarectal formalin application, an effective treatment for grade III haemorrhagic radiation proctitis. Haemorrhagic radiation proctitis (HRP) is infrequently seen amongst the patients who are either undergoing or have undergone radiotherapy to the pelvis. We treated 16 documented cases of HRP, who did not respond to conventional steroid retention e...

Pei, X-jiang.; Hou, Y-bing.; Xu, Z.; Zhao, S-ling.; Teng, F., 2005: Upconversion luminescence properties of YLiF4:Er, Tm, Yb synthesized by hydrothermal method. YLiF4 codoped with Er3+, Tm3+ and Yb3+ ions was synthesized by hydrothermal method. The absorption spectra and upconversion spectra excited at 980 nm were investigated. Under the excitation of infrared photons, strong white emission can be obtaine...

Stella Giannakopoulou; Dimitris Damigos; Dimitris Kaliampakos, 2011: Assessing the economic value of vernacular architecture of mountain regions using contingent valuation. Human pressure on mountain resources poses certain threats to their natural and man-made environment. Although there are many parameters involved, one of the driving forces behind this situation is the emphasis given so far only to the market valu...

Caperelli C.A.; Benkovic P.A.; Demaine M.M.; Benkovic S.J., 1978: Binding and kinetic data for rabbit liver fructose 1 6 bis phosphatase with zinc ion as cofactor. Federation Proceedings 37(6): 1804

Anderson R.V.; Castle S.A.; Delaney J.; Johnson D.R.; Jozefiak A.; Kleuppell R.J.; Peterson R.; Read D.; Tortorello M.L.; E.A., 1973: Cadmium copper lead and zinc trace metal pollution in an aquatic ecosystem. Hill, F Berton Student-Originated Studies Projects, Abstract Reports Presented at Meetings in Washington, D C , U S A Dec 26-29, Vii+279p National Science Foundation: Washington, D C , U S A 90-93

Malabou, C., 2006: Aging and psychological plasticity: contradiction or new therapeutic challenge?. L'encephale 32 Pt 5: S628-S631

Reining P., 1988: How rules for dyads and groups are being used for research on aids. American Association for the Advancement of Science Abstracts of Papers of the National Meeting (154): 88

Madzia, D.; Cau, A., 2017: Inferring 'weak spots' in phylogenetic trees: application to mosasauroid nomenclature. Mosasauroid squamates represented the apex predators within the Late Cretaceous marine and occasionally also freshwater ecosystems. Proper understanding of the origin of their ecological adaptations or paleobiogeographic dispersals requires adequa...

Dubova, E.A.; Klimantsev, I.V.; Pavlov, K.A.; Kulikova, G.V.; Kan, N.E.; Shchyogolev, A.I.; Sukhikh, G.T., 2014: The expression of matrix metalloproteinases in placental tissue depends on the severity of undifferentiated connective tissue dysplasia. Immunohistochemical study of MMP-2 and MMP-9 expression in placental tissue of pregnant patients with undifferentiated connective tissue dysplasia of different severity showed that more severe condition was associated with higher expression of the...

Rocchietta S., 1975: Recent aspects of chronobiology. Bollettino della Societa Italiana di Farmacia Ospedaliera 21(1): 56-61