Plasmalogens Rescue Neuronal Cell Death through an Activation of AKT and ERK Survival Signaling

Abstract

Neuronal cells are susceptible to many stresses, which will cause the apoptosis and neurodegenerative diseases. The precise molecular mechanism behind the neuronal protection against these apoptotic stimuli is necessary for drug discovery. In the present study, we have found that plasmalogens (Pls), which are glycerophospholipids containing vinyl ether linkage at sn-1 position, can protect the neuronal cell death upon serum deprivation. Interestingly, caspse-9, but not caspase-8 and caspase-12, was cleaved upon the serum starvation in Neuro-2A cells. Pls treatments effectively reduced the activation of caspase-9. Furthermore, cellular signaling experiments showed that Pls enhanced phosphorylation of the phosphoinositide 3-kinase (PI3K)-dependent serine/threonine-specific protein kinase AKT and extracellular-signal-regulated kinases ERK1/2. PI3K/AKT inhibitor LY294002 and MAPK/ERK kinase (MEK) inhibitor U0126 treatments study clearly indicated that Pls-mediated cell survival was dependent on the activation of these kinases. In addition, Pls also inhibited primary mouse hippocampal neuronal cell death induced by nutrient deprivation, which was associated with the inhibition of caspase-9 and caspase-3 cleavages. It was reported that Pls content decreased in the brain of the Alzheimer’s patients, which indicated that the reduction of Pls content could endanger neurons. The present findings, taken together, suggest that Pls have an anti-apoptotic action in the brain. Further studies on precise mechanisms of Pls-mediated protection against cell death may lead us to establish a novel therapeutic approach to cure neurodegenerative disorders.

Impact of a Standard Rodent Chow Diet on Tissue n‐6 Fatty Acids, Δ9‐Desaturation Index, and Plasmalogen Mass in Rats Fed for One Year

“…In the case of our healthy rats, at the age of 1 year, the plasmalogen level in the tissues tended to increase, whereas Norton et al showed no major impact of age [55]. Thus, it seems the plasmalogen status does not indicate any defective function in our rat model, while plasmalogens are crucial, for instance, for Schwann cell development and differentiation [59] or as neuroprotective against apoptosis [60], although the role of the alkenyl species remains poorly documented and requires detailed study. Yamazaki showed a structural evolution in plasmenylcholine and plasmenylethanolamine in metabolic syndrome [61].…”

Bone marrow stromal cell–derived exosomes as communicators in drug resistance in multiple myeloma cells

“…49 Inhibition of cleaved caspase-9 and caspase-3 was also found after the treatment with BMSC-derived exosomes. Serum starvation can induce the processing of full-length caspase-8, 50,51 caspase-9, [52][53][54] and caspase-3, 52 and exosomes inhibit the cleavage of caspase-9 to protect these cells from apoptosis. Furthermore, the prosurvival effect of BMSC-derived exosomes was confirmed with exosomes of both ND and MM patients.…”

Involvement of BDNF/ERK signaling in spontaneous recovery from trimethyltin-induced hippocampal neurotoxicity in mice

“…In contrast, there is also accumulating evidence showing that the ERK1/2 pathway is required for neuroprotection (Sanchez et al, 2012). Hossain et al (2013) reported that plasmalogens rescued nutrient deprivation-induced cell death by reducing apoptotic action via activation of Akt and ERK1/2 pathways. In addition, Pignataro et al (2013) demonstrated that ERK1/2 phosphorylation was involved in the neuroprotection produced by remote ischemic post-conditioning.…”