α-cyano-4-hydroxycinnamate decreases both glucose and lactate metabolism in neurons and astrocytes: Implications for lactate as an energy substrate for neurons
✍ Scribed by Mary C. McKenna; Irene B. Hopkins; Adrienne Carey
- Publisher
- John Wiley and Sons
- Year
- 2001
- Tongue
- English
- Weight
- 187 KB
- Volume
- 66
- Category
- Article
- ISSN
- 0360-4012
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
The rates of uptake and oxidation of [U‐^14^C]lactate and [U‐^14^C]glucose were determined in primary cultures of astrocytes and neurons from rat brain, in the presence and absence of the monocarboxylic acid transport inhibitor α‐cyano‐4‐hydroxycinnamate (4‐CIN). The rates of uptake for 1 mM lactate and glucose were 7.45 ± 1.35 and 8.80 ± 1.0 nmol/30 sec/mg protein in astrocytes and 2.36 ± 0.19 and 1.93 ± 0.16 nmol/30 sec/mg protein in neuron cultures, respectively. Lactate transport into both astrocytes and neurons was significantly decreased by 0.25–1.0 mM 4‐CIN; however, glucose uptake was not affected. The rates of ^14^CO~2~ formation from 1 mM lactate and glucose were 12.49 ± 0.77 and 3.42 ± 0.67 nmol/hr/mg protein in astrocytes and 29.32 ± 2.81 and 10.04 ± 1.79 nmol/hr/mg protein in neurons, respectively. Incubation with 0.25 mM 4‐CIN decreased the oxidation of lactate and glucose to 57.1% and 54.1% of control values in astrocytes and to 13.2% and 41.6% of the control rates in neurons, respectively. Preincubation with 4‐CIN further decreased the oxidation of both glucose and lactate. Studies with glucose specifically labeled in the one and six positions demonstrated that 4‐CIN decreased mitochondrial glucose oxidation but did not impair the metabolism of glucose via the pentose phosphate pathway in the cytosol. The lack of effect of 4‐CIN on glutamate oxidation demonstrated that overall mitochondrial metabolism was not impaired. These findings suggest that the impaired neuronal function and tissue damage in the presence of 4‐CIN observed in other studies may be due in part to decreased uptake of lactate; however, the effects of 4‐CIN on mitochondrial transport would significantly decrease the oxidative metabolism of pyruvate derived from both glucose and lactate. © 2001 Wiley‐Liss, Inc.