AJP - Heart AJP: Endocrinology and Metabolism
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol (June 23, 2006). doi:10.1152/ajpheart.01315.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
291/6/H3130    most recent
01315.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hiranandani, N.
Right arrow Articles by Janssen, P. M.L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hiranandani, N.
Right arrow Articles by Janssen, P. M.L.
Submitted on December 14, 2005
Accepted on June 22, 2006

SERCA overexpression reduces hydroxyl radical injury in murine myocardium

Nitisha Hiranandani1, Tepmanas Bupha-Intr2, and Paul M.L. Janssen1*

1 Physiology and Cell Biology, The Ohio State University, Columbus, Ohio, United States
2 Physiology and Cell Biology, The Ohio State University, 43210-1218, Ohio, United States

* To whom correspondence should be addressed. E-mail: janssen.10{at}osu.edu.

Hydroxyl radicals (OH*) are involved in the pathogenesis of ischemia reperfusion injury, and are observed in clinical situations including acute heart failure, stroke and myocardial infarction. Acute transient exposure to OH* causes an intracellular Ca2+ overload and leads to impaired contractility. We investigated whether up-regulation of SR-Ca2+ATPase function (SERCA), can attenuate OH* induced dysfunction. Small, contracting right ventricular papillary muscles from wild type (WT), SERCA1a over-expressing (TG) and SERCA2a heterogeneous knock-out (HET) mice were directly exposed to OH*. This brief 2 minute exposure led to a transient elevation of diastolic force (Fdia), and depression of developed force (Fdev). In WT mice, Fdia increased to 485±49% and Fdev decreased to 11±3%. In sharp contrast, in TG mice Fdia increased only to 241±17% while Fdev decreased only to 51±5% (P<0.05 vs. WT). In HET mice, Fdia rose more than WT (to 597±20%, P<0.05), while Fdev was reduced in a similar amount. After ~45 min after OH*-exposure, a new steady state was reached; Fdev returned to 37±6% and 32±6% while Fdia came back to 238±28% and 292±17% in WT and HET mice resp. In contrast, the sustained dysfunction was significantly less in TG mice: Fdia and Fdev returned to 144±20% and 67±6% resp. Before exposure to OH*, there is decrease in PLB phosphorylation at Ser16 (pPLBSer16) and PLB phosphorylation at Thr17 (pPLBThr17) in TG mice and an increase in pPLBSer16 and pPLBThr17 in HET mice vs. WT. After exposure to OH* there is decrease in pPLBSer16 in WT, TG and HET mice but no significant change in the level of pPLBThr17 in any group. The results indicate that SERCA over-expression can reduce the OH*-induced contractile dysfunction in murine myocardium, whereas a reduced SERCA activity aggravates this injury. Loss of pPLB levels at Ser16 likely amplifies the differences observed in injury response.




This article has been cited by other articles:


Home page
 Circ Heart FailHome page
K. D. Varian, A. Kijtawornrat, S. C. Gupta, C. A.A. Torres, M. M. Monasky, N. Hiranandani, D. A. Delfin, J. A. Rafael-Fortney, M. Periasamy, R. L. Hamlin, et al.
Impairment of Diastolic Function by Lack of Frequency-Dependent Myofilament Desensitizationin Rabbit Right Ventricular Hypertrophy
Circ Heart Fail, September 1, 2009; 2(5): 472 - 481.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
Y. Sun, O. A. Carretero, J. Xu, N.-E. Rhaleb, J. J. Yang, P. J. Pagano, and X.-P. Yang
Deletion of Inducible Nitric Oxide Synthase Provides Cardioprotection in Mice With 2-Kidney, 1-Clip Hypertension
Hypertension, January 1, 2009; 53(1): 49 - 56.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
H. Wang, M. J. Kohr, C. J. Traynham, D. G. Wheeler, P. M. L. Janssen, and M. T. Ziolo
Neuronal nitric oxide synthase signaling within cardiac myocytes targets phospholamban
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1566 - C1575.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. A. H. Talukder, A. Kalyanasundaram, L. Zuo, M. Velayutham, Y. Nishijima, M. Periasamy, and J. L. Zweier
Is reduced SERCA2a expression detrimental or beneficial to postischemic cardiac function and injury? Evidence from heterozygous SERCA2a knockout mice
Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1426 - H1434.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. A. H. Talukder, A. Kalyanasundaram, X. Zhao, L. Zuo, P. Bhupathy, G. J. Babu, A. J. Cardounel, M. Periasamy, and J. L. Zweier
Expression of SERCA isoform with faster Ca2+ transport properties improves postischemic cardiac function and Ca2+ handling and decreases myocardial infarction
Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2418 - H2428.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
N. Hiranandani, S. Raman, A. Kalyanasundaram, M. Periasamy, and P. M. L. Janssen
Frequency-dependent contractile strength in mice over- and underexpressing the sarco(endo)plasmic reticulum calcium-ATPase
Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R30 - R36.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.