Thioredoxin-1 attenuates sepsis-induced cardiomyopathy after cecal ligation and puncture in mice
| Autor: | Mahesh Thirunavukkarasu, Nilanjana Maulik, David W. McFadden, Rickesha L. Wilson, Jacob Campbell, Rajesh Lakshmanan, Vaithinathan Selvaraju |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Survivin Apoptosis Vascular permeability 030204 cardiovascular system & hematology Inhibitor of Apoptosis Proteins Mice chemistry.chemical_compound Thioredoxins 0302 clinical medicine medicine.diagnostic_test Caspase 3 Nitrotyrosine Heart Immunohistochemistry Echocardiography Female Cardiomyopathies TXNIP medicine.medical_specialty animal structures Mice Transgenic Inhibitor of apoptosis Article Capillary Permeability Sepsis Andrology 03 medical and health sciences Western blot Intensive care medicine Animals Aldehydes business.industry Myocardium medicine.disease Surgery Mice Inbred C57BL Repressor Proteins Disease Models Animal Oxidative Stress 030104 developmental biology chemistry Tyrosine Carrier Proteins business Heme Oxygenase-1 |
| Zdroj: | J Surg Res |
| ISSN: | 0022-4804 |
| DOI: | 10.1016/j.jss.2017.06.062 |
| Popis: | Background Sepsis is a leading cause of mortality among patients in intensive care units across the USA. Thioredoxin-1 (Trx-1) is an essential 12 kDa cytosolic protein that, apart from maintaining the cellular redox state, possesses multifunctional properties. In this study, we explored the possibility of controlling adverse myocardial depression by overexpression of Trx-1 in a mouse model of severe sepsis. Methods Adult C57BL/6J and Trx-1Tg/+ mice were divided into wild-type sham (WTS), wild-type cecal ligation and puncture (WTCLP), Trx-1Tg/+sham (Trx-1Tg/+S), and Trx-1Tg/+CLP groups. Cardiac function was evaluated before surgery, 6 and 24 hours after CLP surgery. Immunohistochemical and Western blot analysis were performed after 24 hours in heart tissue sections. Results Echocardiography analysis showed preserved cardiac function in the Trx-1Tg/+ CLP group compared with the WTCLP group. Similarly, Western blot analysis revealed increased expression of Trx-1, heme oxygenase-1 (HO-1), survivin (an inhibitor of apoptosis [IAP] protein family), and decreased expression of thioredoxin-interacting protein (TXNIP), caspase-3, and 3- nitrotyrosine in the Trx-1Tg/+CLP group compared with the WTCLP group. Immunohistochemical analysis showed reduced 4-hydroxynonenal, apoptosis, and vascular leakage in the cardiac tissue of Trx-1Tg/+CLP mice compared with mice in the WTCLP group. Conclusions Our results indicate that overexpression of Trx-1 attenuates cardiac dysfunction during CLP. The mechanism of action may involve reduction of oxidative stress, apoptosis, and vascular permeability through activation of Trx-1/HO-1 and anti-apoptotic protein survivin. |
| Databáze: | OpenAIRE |
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