Inhibition of Akt Attenuates RPO-Induced Cardioprotection

Abstract

Previous studies have shown that red palm oil (RPO) supplementation protected rat hearts against ischaemia-reperfusion injury. Evidence from these studies suggested that Akt may be partly responsible for the observed protection. The aim of the current study was therefore to prove or refute the involvement of Akt in the RPO-induced cardioprotection by administration of a specific Akt inhibitor (A6730). Male Wistar rats were randomly divided into 2 groups: a control group receiving standard rat chow and an experimental group receiving standard rat chow plus 2 mL RPO for six weeks. Hearts were excised and mounted on the Langendorff perfusion system. Functional recovery was documented. A different set of hearts were freeze-clamped to assess total and phosphorylation status of Akt. Another set of hearts were subjected to the same perfusion conditions with addition of A6730. Hearts from this protocol were freeze-clamped and assessed for total and phospho-Akt. RPO improved functional recovery which was associated with increased phosphorylation of Akt on Ser473 and Thr308 residues. Blockade of Akt phosphorylation caused poor functional recovery. For the first time, these results prove that Akt plays an important role in the RPO-induced cardioprotection.

Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level

“…Prior to the evaluation of AKT role in eLTP, we assessed the impact of AKT inhibition on basal synaptic activity in acute hippocampal slices using A6730, a potent AKT inhibitor (Hu et al, ; Katengua‐Thamahane et al, ; Nikhil et al, ; Tomas et al, ; You et al, ). A6730 is highly specific to AKT1 and AKT2 isoforms, while having a minimal impact on AKT3 activity (Lindsley et al, ) and a negligible influence on the activity of other enzymes, in contrast to known pan‐AKT inhibitors (Barnett et al, ).…”

Modulation of Hypercholesterolemia‐Induced Oxidative/Nitrative Stress in the Heart

“…They showed that prolonged dietary feeding with RPO-supplemented diet (~7 g RPO/kg diet) protected the heart against ischemia/reperfusion injury in rats. They used isolated heart models, perfused both in Langendorff technique [ 215 – 218 ] and working mode [ 212 , 219 ], showing the vascular-independent direct cardioprotective effects of RPO. RPO administration improved cardiac function during reperfusion [ 212 ] and decreased infarct size [ 215 , 216 ].…”

Effects of Red Palm Oil on Myocardial Antioxidant Enzymes, Nitric Oxide Synthase and Heart Function in Spontaneously Hypertensive Rats

“…It is of interest to researchers that new approaches include those that target mitochondrial function and energetic as well as prevention of no-reflow phenomenon [ 43 ]. Besides prevention of excessive ROS, one of the possible mechanisms by which RPO might confer cardiovascular protection during ischemia/reperfusion is via increased phosphorylation of Akt kinase [ 19 , 21 ]. This activation might be especially important in the heart of SHR where the basal NOS activity was significantly elevated [ 44 ].…”

“…Antibodies were purchased from Cell Signalling (Danvers, MA, USA) and Abcam (Cambridge, UK). Other chemicals were obtained from Bio-RAD and Sigma (St. Louis, MO, USA) [ 21 ].…”

“…It has been reported that antioxidant-rich red palm oil (RPO) exerts cardio-protection against ischaemia reperfusion injury [ 19 , 20 , 21 ]. It is probably due to its ratio of saturated/unsaturated fatty acid and high phytonutrients concentration.…”