Inhibition of SGLT1 abrogates preconditioning-induced cardioprotection against ischemia-reperfusion injury

Abhinav Kanwal, Hina L. Nizami, Surekha Mallapudi, Uday Kumar Putcha, G. Krishna Mohan, Sanjay K. Banerjee

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Abstract

Background Recently, we reported Na+/glucose co-transporter (SGLT1) expression in mouse and human heart. We speculated that SGLT1 might play an important role in ischemic preconditioning-induced cardioprotection. Therefore, the present study was designed to find the role of SGLT1 in ischemic preconditioning-induced cardioprotection. Methods Hearts isolated from SD male rats were subjected to either ischemia-reperfusion injury (I/R) (15 min global ischemia followed by 20 min reperfusion) or ischemic preconditioning (IPC) (3 cycles of 2 min global ischemia separated by 3 min reperfusion) followed by I/R in presence and absence of phlorizin, an SGLT1 inhibitor. Results IPC increased membrane SGLT1 expression in rat heart as observed by immunoblotting and immunohistochemistry. Hearts from I/R group showed significant increase in oxidative stress levels and marked myocardial injury as compared to control. We also observed significant increase in apoptotic parameters in I/R heart, as measured by caspase-3 activity, TUNEL positive nuclei and gene expression analysis. Significant improvement in oxidative stress, apoptosis parameters and cardiac injury was observed in I/R hearts when subjected to IPC. However, all beneficial effects of preconditioning were lost when hearts were pre-treated with phlorizin. Conclusion Present study indicated that inhibition of SGLT1 by phlorizin abrogated the beneficial effect of ischemic-preconditioning and for the first time, provides evidence that SGLT1 plays a crucial role in ischemic preconditioning-induced cardioprotection.

Original languageEnglish
Pages (from-to)392-398
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume472
Issue number2
DOIs
Publication statusPublished - 01-04-2016

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All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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