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Kenjiro Muta


kenjiro-muta@uiowa.edu
Mentor: Kamal Rahmouni, Ph.D.
Lab Room: 3125 MERF
Lab Phone: 319-335-7895

The signaling mechanisms of hypothalamic Angiotensin II-induced renal sympathetic nerve activity

Angiotensin II (AngII) is a bio-active peptide which is produced systemically and locally in various tissues including brain, kidney and vasculature, regulating blood pressure in acute or long-term manner. It has been known that hypothalamic AngII receptor signaling pathway controls blood pressure by activating sympathetic nervous system innervating kidney. However, the signaling mechanism of AngII in hypothalamus in regulation of blood pressure remains unclear. As previously reported by our lab and others, both hypothalamic leptin and insulin remarkably increases renal sympathoactivity through PI3K/mTOR pathway. In addition, it has been reported that AngII induces activation of PI3K/mTOR pathway via transactivation of EGF receptor in smooth muscle cells and cardiac myocytes. These results suggest that hypothalamic AngII may cause sympathoactivation of kidney through PI3K/mTOR pathway, eventually leading to hypertension. To reveal this signaling pathway, I utilize GT1-7 cells (hypothalamic neuroblastoma cells) transfected with type 1 AngII receptor to see whether AngII induces phosphorylation of several components of PI3K/mTOR signaling such as Akt, mTOR, S6 kinase and ribosomal protein S6, which may regulate production of neuropeptides involved with renal sympathoactivity.

Publications:

Zhong J, Yang P, Muta K, Dong R, Marrero M, Gong F, Wang CY. Loss of Jak2 selectively suppresses DC-mediated innate immune response and protects mice from lethal dose of LPS-induced septic shock. PLoS One. 5(3):e9593, 2010.

Ali MI, Ketsawatsomkron P, Belin de Chantemele EJ, Mintz JD, Muta K, Salet C, Black SM, Tremblay ML, Fulton DJ, Marrero MB, Stepp DW. Deletion of protein tyrosine phosphatase 1b improves peripheral insulin resistance and vascular function in obese, leptin-resistant mice via reduced oxidant tone. Circ Res. 105(10):1013-22, 2009.

Belin de Chantemèle EJ, Muta K, Mintz J, Tremblay ML, Marrero MB, Fulton DJ, Stepp DW. Protein tyrosine phosphatase 1B, a major regulator of leptin-mediated control of cardiovascular function. Circulation. 120(9):753-63, 2009.

Kuroyanagi Y, Kaneko Y, Muta K, Park BS, Moi P, Ausenda S, Cappellini MD, Ikuta T. cAMP differentially regulates gamma-globin gene expression in erythroleukemic cells and primary erythroblasts through c-Myb expression. Biochem Biophys Res Commun. 344(3):1038-47, 2006.

Abstracts:

Belin de Chantemele EJ, Marrero MB, Muta K, Lilly B, Inscho EW, Fulton D, Stepp DW. Protein tyrosine phosphatase 1B (PTP1B): a major regulator of leptin-mediated control of cardiovascular function. Experimental Biology 2009, New Orleans

Ketsawatsomkron P, Belin de Chantemele E, Muta K, Fulton D, Stepp D, Marrero M. Regulation of vascular insulin signaling by protein tyrosine phosphatase 1B (PTP1B) in mouse models of obesity. Experimental Biology 2008, San Diego



Honors and Awards

  • Graduate Student Senate Travel Funds 2012
  • AHA Predoctoral Fellowship