Recent studies have shown that a brief exposure to ischemia renders the heart better able to tolerate a subsequent longer ischemic insult, a phenomenon called ischemic preconditioning. The first hypothesis of this proposal is that ischemic preconditioning is accompanied by enhanced and sustained gene expression of HSPs in the heart of rats and rabbits. In addition to HSP70, the applicants will explore the role of other stress proteins such as HSP27, 60, and 90. The second hypothesis is that quercitine, an inhibitor of the heat shock transcription factor, blocks preconditioning by blocking the synthesis of HSPs. The third hypothesis is that oxygen radicals directly trigger the preconditioning and that scavenging of radicals by antioxidants attenuates the protection derived from preconditioning and reduces the expression of HSPs. The fourth hypothesis is that activation of adenosine A1-receptors during preconditioning results in enhanced expression of HSPs. The applicants will examine the effects of adenosine agonists and antagonists on preconditioning and HSP synthesis in rats as well as rabbits. The fifth hypothesis is that synthesis of HSPs mediates the second window of protection which develops 24 hours after ischemic preconditioning. The applicants anticipate answering the following questions: (1) whether preconditioning induces the expression of HSP27, 60, and 90 in addition to HSP70; (2) whether HSPs are involved in preconditioning early or late; (3) whether oxygen radicals trigger the preconditioning by inducing HSP; and (4) whether adenosine receptor activation induces expression of HSPs resulting in preconditioning.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL051045-04
Application #
2735223
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1995-08-01
Project End
1999-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
4
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Virginia Commonwealth University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Richmond
State
VA
Country
United States
Zip Code
23298
Nagiub, Mohamed; Filippone, Scott; Durrant, David et al. (2017) Long-acting PDE5 inhibitor tadalafil prevents early doxorubicin-induced left ventricle diastolic dysfunction in juvenile mice: potential role of cytoskeletal proteins. Can J Physiol Pharmacol 95:295-304
Kura, B; Yin, C; Frimmel, K et al. (2016) Changes of microRNA-1, -15b and -21 levels in irradiated rat hearts after treatment with potentially radioprotective drugs. Physiol Res 65 Suppl 1:S129-37
Das, Sayantanee; Filippone, Scott M; Williams, Denise S et al. (2016) Beet root juice protects against doxorubicin toxicity in cardiomyocytes while enhancing apoptosis in breast cancer cells. Mol Cell Biochem 421:89-101
Das, Anindita; Durrant, David; Mitchell, Clint et al. (2016) Sildenafil (Viagra) sensitizes prostate cancer cells to doxorubicin-mediated apoptosis through CD95. Oncotarget 7:4399-413
Gill, Rabia; Kuriakose, Robin; Gertz, Zachary M et al. (2015) Remote ischemic preconditioning for myocardial protection: update on mechanisms and clinical relevance. Mol Cell Biochem 402:41-9
Das, Anindita; Samidurai, Arun; Hoke, Nicholas N et al. (2015) Hydrogen sulfide mediates the cardioprotective effects of gene therapy with PKG-I?. Basic Res Cardiol 110:42
Salloum, Fadi N; Sturz, Gregory R; Yin, Chang et al. (2015) Beetroot juice reduces infarct size and improves cardiac function following ischemia-reperfusion injury: Possible involvement of endogenous H2S. Exp Biol Med (Maywood) 240:669-81
Das, Anindita; Salloum, Fadi N; Filippone, Scott M et al. (2015) Inhibition of mammalian target of rapamycin protects against reperfusion injury in diabetic heart through STAT3 signaling. Basic Res Cardiol 110:31
Shalwala, Mona; Zhu, Shu-Guang; Das, Anindita et al. (2014) Sirtuin 1 (SIRT1) activation mediates sildenafil induced delayed cardioprotection against ischemia-reperfusion injury in mice. PLoS One 9:e86977
Das, Anindita; Durrant, David; Koka, Saisudha et al. (2014) Mammalian target of rapamycin (mTOR) inhibition with rapamycin improves cardiac function in type 2 diabetic mice: potential role of attenuated oxidative stress and altered contractile protein expression. J Biol Chem 289:4145-60

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