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Carbon monoxide improves neuronal differentiation and yield by increasing the functioning and number of mitochondria
Author(s) -
Almeida Ana S.,
Sonnewald Ursula,
Alves Paula M.,
Vieira Helena L.A.
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13653
Subject(s) - citric acid cycle , mitochondrion , glycolysis , biology , oxidative phosphorylation , microbiology and biotechnology , biochemistry , population , metabolism , cellular differentiation , demography , sociology , gene
The process of cell differentiation goes hand‐in‐hand with metabolic adaptations, which are needed to provide energy and new metabolites. Carbon monoxide ( CO ) is an endogenous cytoprotective molecule able to inhibit cell death and improve mitochondrial metabolism. Neuronal differentiation processes were studied using the NT 2 cell line, which is derived from human testicular embryonic teratocarcinoma and differentiates into post‐mitotic neurons upon retinoic acid treatment. CO ‐releasing molecule A1 ( CORM ‐A1) was used do deliver CO into cell culture. CO treatment improved NT 2 neuronal differentiation and yield, since there were more neurons and the total cell number increased following the differentiation process. CO supplementation enhanced the mitochondrial population in post‐mitotic neurons derived from NT 2 cells, as indicated by an increase in mitochondrial DNA . CO treatment during neuronal differentiation increased the extent of the classical metabolic change that occurs during neuronal differentiation, from glycolytic to more oxidative metabolism, by decreasing the ratio of lactate production and glucose consumption. The expression of pyruvate and lactate dehydrogenases was higher, indicating an augmented oxidative metabolism. Moreover, these findings were corroborated by an increased percentage of 13 C incorporation from [U‐ 13 C]glucose into the tricarboxylic acid cycle metabolites malate and citrate, and also glutamate and aspartate in CO ‐treated cells. Finally, under low levels of oxygen (5%), which enhances glycolytic metabolism, some of the enhancing effects of CO on mitochondria were not observed. In conclusion, our data show that CO improves neuronal and mitochondrial yield by stimulation of tricarboxylic acid cycle activity, and thus oxidative metabolism of NT 2 cells during the process of neuronal differentiation.The process of cell differentiation is coupled with metabolic adaptations. Carbon monoxide (CO) is an endogenous cytoprotective gasotransmitter able to prevent cell death and improve mitochondrial metabolism. Herein CO supplementation improved neuronal differentiation yield, by enhancing mitochondrial population and promoting the classical metabolic change that occurs during neuronal differentiation, from glycolytic to oxidative metabolism.