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Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB

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Cell Stress and Chaperones Aims and scope

Abstract

It has been reported that pretreatment of rats with lipopolysaccharide (LPS) increases myocardial functional recovery in ischemia/reperfusion (I/R) hearts. However, the mechanisms by which LPS induces cardioprotection against I/R injury have not been fully elucidated. In this study, we pretreated rats with LPS (1.0 mg/kg) 24 h before they were subjected to I/R injury, and then examined the roles of heat shock protein-70 (HSP70) and nucleus factor-κB (NF-κB) in LPS-induced cardioprotection. We observed that pretreatment with low-dose LPS resulted in significantly increased levels of HSP70 in the myocardium, which could dramatically inhibit NF-κB translocation and reduce degradation of inhibitory κB. Inhibition of NF-κB, in turn, attenuated release of inflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-1β, and IL-6) and reduced apoptosis of myocardium and infarct area following I/R injury. Moreover, HSP70 could ameliorate oxidative stress following I/R injury. To further investigate whether increase of HSP70 might be responsible for protection of the myocardium against I/R injury, we co-administered the HSP70 inhibitor, quercetin, with LPS before I/R injury. We found that LPS-induced cardioprotection was attenuated by co-administration with quercetin. Herein, we concluded that increased levels of HSP70 through LPS pretreatment led to inhibition of NF-κB activity in the myocardium after I/R injury. Our results indicated that LPS-induced cardioprotection was mediated partly through inhibition of NF-κB via increase of HSP70, and LPS pretreatment could provide a means of reducing myocardial I/R injury.

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Acknowledgments

This project was supported by grants from the Technology Bureau Foundation of Zhenjiang City, Jiangsu Province (No. SH2008043).

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Authors and Affiliations

  1. Department of Cardiology, Affiliated People’s Hospital of Jiangsu University, No.8, DianLi Road, Zhenjiang, Jiangsu Province, 212000, People’s Republic of China

    Yong-wei Yao, Guo-hui Zhang, Ying-yu Zhang, Wei-dong Li, Cheng-hua Wang & Chun-yang Yin

  2. Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029, People’s Republic of China

    Fu-min Zhang

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  1. Yong-wei Yao
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  2. Guo-hui Zhang
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  3. Ying-yu Zhang
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  6. Chun-yang Yin
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Correspondence to Guo-hui Zhang.

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Yao, Yw., Zhang, Gh., Zhang, Yy. et al. Lipopolysaccharide pretreatment protects against ischemia/reperfusion injury via increase of HSP70 and inhibition of NF-κB. Cell Stress and Chaperones 16, 287–296 (2011). https://doi.org/10.1007/s12192-010-0242-6

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  • DOI: https://doi.org/10.1007/s12192-010-0242-6

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