Emel Songu-Mize, PhD
The research interests included elucidating the mechanisms underlying the changes in blood pressure, primarily the regulation of vascular Na+, K+-ATPase (the Na-pump) activity and the contribution of this enzyme to development and maintenance of hypertension, a widespread health problem in this country. We have characterized the Na+, K+-ATPase isoforms in vascular smooth muscle cells, and explored the cellular mechanisms participating in the regulation of these isoforms using an in vitro model system and cultured aortic smooth muscle cells. Using Flexercell Apparatus, a computer-driven device that allows application of cyclic acute or chronic mechanical strain to the cells in culture, we have reported that expression of both the alpha-1 and alpha-2 catalytic subunits of the Na+, K+- adenosinetriphosphatase (Na+, K+-ATPase) is elevated after a 2 to 4 day chronic cyclic stretch regimen in aortic smooth muscle cells. A short-term regimen, 2 to 30 minutes of stretch, also caused a stimulation of the activity of the enzyme, measured as active transport of Rb(+K) into the cell. An elevation of intracellular Na accompanied the increase in pump activity. Blocking the stretch-activated channels or Na/H exchange pump did not affect the stretch-induced increase in Na-pump activity. Inhibiting PKA activity prior to stretch had a small but significant effect on stretch-induced increase in Na-pump activity. However, inhibition of polymerization of actin with cytochalasin D prevented this effect. Wortmannin, a PI-3 kinase inhibitor, also prevented this action of stretch on Na-pump activity, suggesting a mechanism involving the cytoskeleton and endosomal transport. This effect of stretch may be part of a compensatory mechanism during episodes of increased intramural pressure.
We also investigated whether application of stretch affects expression of the genes encoding the alpha-1 and alpha-2 subunits of the Na+, K+-ATPase. We collected data suggesting transcriptional regulation of the alpha subunits in response to stretch. There was a differential response to the degree of stretch between the two isoforms. Differential regulation of the catalytic isoforms of the vascular smooth muscle cell Na+, K+-ATPase by stretch may have important implications in response of the blood vessels to pathophysiological changes in disease states such as essential hypertension.
In addition, the regulation of TrpC family of proteins that constitute certain types of calcium channels is of interest. We investigated calcium handling in smooth muscle cells and the behavior of TrpC3 to -5 channels in terms of intracellular calcium levels and functional consequences after exposure to chronic cyclic stretch.
Lindsey SH, Songu-Mize E.Stretch-Induced TRPC4 downregulation is accompanied by reduced capacitative Ca2+ entry in WKY but not SHR mesenteric smooth muscle cells.Clin Exp Hypertens. 32(5):288-92, 2010.
Lindsey-Hoffmann SE, Tribe RM, and Songu-Mize E., Cyclic stretch modulates TRPC4 expression and function in rat aortic and mesenteris smooth muscle cells.Life Sciences: 83, 29-34, 2008.
Dalrymple, A, Mahn, K Poston, L Songu-Mize E, and Tribe, RM. Mechanical strech regulates TrpC proteins and calcium entry in human myometrial smooth muscle cells.Molecular Human Reproduction, 00:42-46, 2007.
Ark M, Kubat H, Beydağı H, Ergenoğlu T and Songu-Mize E., Involvement of rho kinase in the ouabain-induced contractions of the rat renal arteries, Biochem. Biophys Res Comm 340: 417-421, 2006.
Ark M, Ozveren E, Yazici G, Korkmaz B, Buyukafsar K, Arikan O, Kubat H, Songu-Mize E., Effect of HA-1077,and Y-27632, two rho-kinase inhibitors, in human umbilical artery, Cell Biochem. Biophys. 41:331-342, 2004.
Sevieux N, Ark M, Hornick C, Songu-Mize E, Short-term stretch translocates the alpha-1 subunit of the Na-pump to plasma membrane., Cell Biochemistry and Bio-physics 38: 23-32, 2003.
Songu-Mize E, Sevieux N, Liu X, Jacobs M, Effect of short-term cyclic stretch on sodium pump activity in aortic smooth muscle cells., Amer J Physiol (Heart and Circ. Physiol.) 281:H2072-H 2078, 2001.
Sevieux S, Alam J, Songu-Mize E, Effect of cyclic stretch on alpha subunit mRNA expression of Na+,K+-ATPase in aortic smooth muscle cells., Amer J Physiology (Cell Physiol) 280: C1555-C1560, 2001.
Professional and Scholarly Activities
Membership on Study Section Panels and other National Appointments
NIH/HLB, Member Special Panel, 2005
Member, NIH Cardiovascular and Renal Study Section, 1999-2003
Special Reviewer, National Science Foundation (NSF), 2000
Special Reviewer, U.S. Civilian Research and Development Foundation (CRDF), 2000
Special Reviewer, NIH Cardiovascular and Renal Study Section, 1993, 1994, 1996, 1999
Special Reviewer, NIH Experimental Cardiovascular Study Section, 1997
Member, Cardiovascular Regulation II Study Committee, American Heart Association, 1995-1999
Member, Committee on Professional and Public Education, AHA, Council for High Blood Pressure, 2002-2004
Member, Directors of Pharmacology Programs Committee, 2004-Present
ASPET, Counselor and Member, Executive Committee, Cardiovascular Pharmacology Section, 2004-2006
ASPET, Member, Competition Committee for the Division of Cardiovascular Pharmacology, 2006-Present
Students and Fellows Trained at LSUHSC
Caren Carpi - SUN Program Student, Summer 1994
Courtney Schiro - SUN Program Student, Summer 1995
Janet Stones - Graduate Student, Research Rotation, 1995
Sam Park - Kalamazoo Collage, Student Intern, 1996
Najy Masri - SUN Program Student, Summer 1996
Shawn Wiltse - Kalamazoo Collage, Student Intern, 1997
Amber Moreau - SUN Program Student, Summer 1997
Ashley Shreves - SUN Program Student, Summer 1998
Ze Zhang – LA Cancer Research Consortium, Summer Research Intern, 2004
Ivante Jackson – LA Cancer Research Consortium, Summer Research Intern, 2004
Xiang Liu - PhD Dissertation Advisor, 1993-1997, Ph.D. 1997
Nancy Sevieux, MS– PhD Dissertation Advisor, 1997-2002, Ph.D. 2002
Renee Bergeron – Dissertation Committee Member, 1991-1993
Arif Hasan – Dissertation Committee Member, Department of Physiology, 1994-1996
Shuxin Zhang – Dissertation Committee Member, 1999-2001
Dongdong Yao - Dissertation Committee Member, 1999-2001
Naili Duan - Qualifiying Exam Committee Member, 1993.
Sena Sezen MS - Research, 1993-1995
Eser Ercil, MS - Research 1998-1999
Zhihong Zhang - Research Rotation, 1992
Dixie Louviere – Research Rotation, 2000
Zhen He – Thesis Advisor, 2000-2002 (MS: December 2002)
Melissa Burmeister – Research Rotation, 2002
Yuri Peterson – Dissertation Committee Member, (PhD: December 2004)
Sarah Hoffmann –Dissertation Advisor, 2003-2007, Ph.D. 2007
Erica Williams –Research Rotation, 2003 Summer
Michael Monroe –Dissertation Advisor (PhD: December 2003)
Russell Kelley –Dissertation Committee Member (PhD: December 2004)
Jody Arsenault – Graduate Student, Dissertation Committee Member. 2002-2005
Anna Dunne – Graduate Student, Examination Committee, and Dissertation Committee member, 2003-2007
Diana DeCoster – Graduate Student, Examination Committee Member, 2004-2006
Kartic Rajput – Graduate Student, Examination Committee Member, 2004-2007
Dr. SaharRashed, Postdoctoral Fellow, 1991 – 1995
Dr. Inci Erdemli, Professor of Pharmacology, Visiting Research Scholar, AnkaraTurkey, 1992-1993
Dr. Dalton Vassallo, Chairman and Professor of Physiology, Visiting Scholar, Vitoria, Brazil, 1994
Dr. Mustafa Ark, Associate Professor, TUBITAK/NATO Fellow from Gazi University, Ankara, Turkey, 2001