Mitochondria damaged by Oxygen Glucose Deprivation can be Restored through Activation of the PI3K/Akt Pathway and Inhibition of Calcium Influx by Amlodipine Camsylate

Abstract

Amlodipine, a L-type calcium channel blocker, has been reported to have a neuroprotective effect in brain ischemia. Mitochondrial calcium overload leads to apoptosis of cells in neurologic diseases. We evaluated the neuroprotective effects of amlodipine camsylate (AC) on neural stem cells (NSCs) injured by oxygen glucose deprivation (OGD) with a focus on mitochondrial structure and function. NSCs were isolated from rodent embryonic brains. Effects of AC on cell viability, proliferation, level of free radicals, and expression of intracellular signaling proteins were assessed in OGD-injured NSCs. We also investigated the effect of AC on mitochondrial structure in NSCs under OGD by transmission electron microscopy. AC increased the viability and proliferation of NSCs. This beneficial effect of AC was achieved by strong protection of mitochondria. AC markedly enhanced the expression of mitochondrial biogenesis-related proteins and mitochondrial anti-apoptosis proteins. Together, our results indicate that AC protects OGD-injured NSCs by protecting mitochondrial structure and function. The results of the present study provide insight into the mechanisms underlying the protective effects of AC on NSCs.

Melatonin reshapes the mitochondrial network and promotes intercellular mitochondrial transfer via tunneling nanotubes after ischemic‐like injury in hippocampal HT22 cells

“…Although the reason of this discrepancy is not clear, we found conflicting results in the literature regarding PGC1α expression after OGD/R, which was found increased in some experimental models 47 , 48 but not in others. 49 , 50 Nevertheless, the concomitant increase in SIRT3/PGC1α after melatonin treatment indicates that the SIRT3/PGC1α pathway may be involved in its protective effect, as suggested by previous studies. 38 , 39 Our findings also show that melatonin upregulates the expression of mitochondrial fusion‐related factors, such as MFN2 and OPA1.…”

Are antibacterial effects of non-antibiotic drugs random or purposeful because of a common evolutionary origin of bacterial and mammalian targets?

“…Could a combination of non-antibiotics with antibiotics both carrying mitochondrial liabilities increase or decrease their individual effects on mitochondrial functions? Calcium antagonists [251][252][253][254][255] and ACE-inhibitors [256][257][258][259][260] reduced respiration and ATP synthesis. Sorafenib directly impaired mitochondrial function at clinically relevant concentrations [261] whereas imatinib lacked direct mitochondrial effects but affected mitochondrial functions via altered kinase and other signalling pathways [261,262].…”

Effect of amlodipine on cytosolic calcium and apoptosis in hyperglycemia induced-human neuronal cell line culture

“…Amlodipine administration in hyperglycemia induced cell Therefore, amlodipine could protect OGD injured NSC by maintaining function and structure of mitochondria. Amlodipine protected OGD -injured NSC by inhibiting mitochondrial calcium in ux, activate the PI3K pathway and maximized protein biogenesis [16].…”