In:
ASN Neuro, SAGE Publications, Vol. 6, No. 5 ( 2014-07-01), p. 175909141455099-
Abstract:
Exogenous ketone bodies (KBs), acetoacetate (AA), and β-hydroxybutyrate (BHB) act as alternative energy substrates in neural cells under starvation. The present study examined the endogenous ketogenic capacity of astroglia under hypoxia with/without glucose and the possible roles of KBs in neuronal energy metabolism. Cultured neurons and astroglia were prepared from Sprague-Dawley rats. Palmitic acid (PAL) and l-carnitine (LC) were added to the assay medium. The 4- to 24-hr production of AA and BHB was measured using the cyclic thio-NADH method. 14 C-labeled acid-soluble products (KBs) and 14 CO 2 produced from [1- 14 C]PAL were also measured. l-[U- 14 C]lactic acid ([ 14 C]LAC), [1- 14 C]pyruvic acid ([ 14 C]PYR), or β-[1- 14 C]hydroxybutyric acid ([ 14 C]BHB) was used to compare the oxidative metabolism of the glycolysis end products with that of the KBs. Some cells were placed in a hypoxic chamber (1% O 2 ). PAL and LC induced a higher production of KBs in astroglia than in neurons, while the CO 2 production from PAL was less than 5% of the KB production in both astroglia and neurons. KB production in astroglia was augmented by the AMP-activated protein kinase activators, AICAR and metformin, as well as hypoxia with/without glucose. Neuronal KB production increased under hypoxia in the absence of PAL and LC. In neurons, [ 14 C]LAC and [ 14 C]PYR oxidation decreased after 24 hr of hypoxia, while [ 14 C]BHB oxidation was preserved. Astroglia responds to ischemia in vitro by enhancing KB production, and astroglia-produced KBs derived from fatty acid might serve as a neuronal energy substrate for the tricarboxylic acid cycle instead of lactate, as pyruvate dehydrogenase is susceptible to ischemia.
Type of Medium:
Online Resource
ISSN:
1759-0914
,
1759-0914
DOI:
10.1177/1759091414550997
Language:
English
Publisher:
SAGE Publications
Publication Date:
2014
detail.hit.zdb_id:
2485467-0
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