Drug Design, Development and Therapy (Sep 2016)
Protein kinase C–mediated sodium glucose transporter 1 activation in precondition-induced cardioprotection
Abstract
Abhinav Kanwal,1,2 Sujatha Kasetti,3 Uday Kumar Putcha,4 Shailendra Asthana,2 Sanjay K Banerjee1,2 1Division of Medicinal Chemistry and Pharmacology, Indian Institute of Chemical Technology, Hyderabad, India; 2Drug Discovery Research Center (DDRC), Translational Health Science and Technology Institute (THSTI), Faridabad, Haryana, India; 3Department of Pharmacology, National Institute of Pharmaceutical Education and Research, Hyderabad, India; 4Department of Pathology, National Institute of Nutrition, Hyderabad, India Abstract: The concept of cardioprotection through preconditioning against ischemia–reperfusion (I/R) injury is well known and established. However, among different proposed mechanisms regarding the concept of ischemic preconditioning, protein kinase C (PKC)-mediated cardioprotection through ischemic preconditioning plays a key role in myocardial I/R injury. Thus, this study was designed to find the relationship between PKC and sodium glucose transporter 1 (SGLT1) in preconditioning-induced cardioprotection, which is ill reported till now. By applying a multifaceted approach, we demonstrated that PKC activates SGLT1, which curbed oxidative stress and apoptosis against I/R injury. PKC activation enhances cardiac glucose uptake through SGLT1 and seems essential in preventing I/R-induced cardiac injury, indicating a possible cross-talk between PKC and SGLT1. Keywords: ischemic preconditioning, ischemia-reperfusion injury, phorbol-12-myristate, oxidative stress, SGLT1, phlorizin
