Emel Songu-Mize, PhD
Research
Current Laboratory Group:
The research is directed at
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 his enzyme to development and
maintenance of hypertension, a widespread health problem in this country. In
recent years we have characterized the Na+, K+-ATPase
isoforms in vascular smooth muscle cells, and are now
exploring 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 a-1 and a-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, 2-30 min 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 a-1
and a-2 subunits of the Na+, K+-ATPase. We recently
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 2 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.
Selected Publications
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,
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
Undergraduate Students:
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
Graduate Students:
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-Present
Diana DeCoster – Graduate Student, Examination
Committee Member, 2004-2006
Kartic Rajput –
Graduate Student, Examination Committee Member, 2004-Present
Postdoctoral Fellows:
Dr. Sahar
Rashed, Postdoctoral Fellow, 1991 – 1995
Visiting Scientists:
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