Green tea attenuates angiotensin II-induced cardiac hypertrophy in rats by modulating reactive oxygen species production and the Src/epidermal growth factor receptor/Akt signaling pathway.
We previously documented a clear-cut antihypertensive effect of green teat extract (GTE), which was associated with correction of endothelial dysfunction and prevention of left ventricular hypertrophy in an angiotensin II (Ang II)-dependent model of hypertension, but the molecular mechanisms remain to be defined. As several effects of Ang II involve production of reactive oxygen species (ROS) and activation of 2nd messengers, such as mitogen-activated protein kinase (MAPK) and Akt, we investigated the effect of GTE on these signal transduction pathways in Ang II-treated rats. Rats were treated for 2 wk with Ang II infusion (700 mug.kg(-1).d(-1); n = 6, via osmotic minipumps), Ang II plus GTE (6 g/L) dissolved in the drinking water; n = 6), or vehicle (n = 6) to serve as controls. Blood pressure was monitored by telemetry throughout the study. The activation and expression of NAD(P)H oxidase subunits, protein kinase C isoforms, Src, epidermal growth factor receptor (EGFR), Akt, and MAPK were determined in the heart in vitro through immunoprecipitation and western blot analysis with specific antibodies. NAD(P)H oxidase enzymatic activity was measured by cytochrome c reduction assay. GTE blunted Ang II-induced blood pressure increase and cardiac hypertrophy. In Ang II-treated rats, GTE decreased the expression of the NAD(P)H oxidase subunit gp91(phox) and the translocation of Rac-1, as well as NAD(P)H oxidase enzymatic activity. Furthermore, it specifically reduced Ang II-induced Src, EGFR, and Akt phosphorylation. These results show that GTE blunts Ang II-induced cardiac hypertrophy specifically by regulating ROS production and the Src/EGFR/Akt signaling pathway activated by Ang II.
Papparella
Italia
I
Department of Clinical and Experimental Medicine and Experimental Biomedical Sciences, University of Padova, 35128 Padova, Italy.
Ceolotto
Giulio
G
Montemurro
Domenico
D
Antonello
Michele
M
Garbisa
Spiridione
S
Rossi
Gianpaolo
G
Semplicini
Andrea
A
D000804:Angiotensin II / Q000633:toxicity; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D007527:Isoenzymes; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013662:Tea; D019061:src-Family Kinases / Q000378:metabolism*
D007527:Isoenzymes; D021122:Protein Subunits; D017382:Reactive Oxygen Species; D013662:Tea; D000804:Angiotensin II; D019255:NADPH Oxidases; D066246:ErbB Receptors; D019061:src-Family Kinases; D051058:Oncogene Protein v-akt; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases