Pulsed electromagnetic field and relief of hypoxia‐induced neuronal cell death: The signaling pathway
Low‐energy low‐frequency pulsed electromagnetic fields (PEMFs) exert several protective effects, such as the regulation of kinases, transcription factors as well as cell viability in both central and peripheral biological systems. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown.
In this study, we have characterized in nerve growth factor‐differentiated pheochromocytoma PC12 cells injured with hypoxia: (i) the effects of PEMF exposure on cell vitality; (ii) the protective pathways activated by PEMFs to relief neuronal cell death, including adenylyl cyclase, phospholipase C, protein kinase C epsilon and delta, p38, ERK1/2, JNK1/2 mitogen‐activated protein kinases, Akt and caspase‐3; (iii) the regulation by PEMFs of prosurvival heat‐shock proteins of 70 (HSP70), cAMP response element‐binding protein (CREB), brain‐derived neurotrophic factor (BDNF), and Bcl‐2 family proteins. The results obtained in this study show a protective effect of PEMFs that are able to reduce neuronal cell death induced by hypoxia by modulating p38, HSP70, CREB, BDNF, and Bcl‐2 family proteins. Specifically, we found a rapid activation (30 min) of p38 kinase cascade, which in turns enrolles HSP70 survival chaperone molecule, resulting in a significant CREB phosphorylation increase (24 hr). In this cascade, later (48 hr), BDNF and the antiapoptotic signaling pathway regulated by the Bcl‐2 family of proteins are recruited by PEMFs to enhance neuronal survival.
This study paves the way to elucidate the mechanisms triggered by PEMFs to act as a new neuroprotective approach to treat cerebral ischemia by reducing neuronal cell death.
Stefania Gessi, Stefania Merighi, Serena Bencivenni, Enrica Battistello, Fabrizio Vincenzi, Stefania Setti, Matteo Cadossi, Pier Andrea Borea, Ruggero Cadossi, Katia Varani. Journal of Cellular Physiology, January 17, 2019, https://doi.org/10.1002/jcp.28149.