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Indian Journal of Experimental Biology (IJEB) >
IJEB Vol.48 [2010] >
IJEB Vol.48(06) [June 2010] >
| Title: | Changes in cytosolic Ca2+ levels correspond to fluctuations of lactate levels in crosstalk of astrocyte-neuron cell lines |
| Authors: | Ghosh, Shantanu
Kaushik, Deepak K
Gomes, James
Nayeem, Shahid
Deep, Shashank
Basu, Anirban |
| Keywords: | ANLS
Calcium upregulation
Cerebral vasoregulation
Isoenzyme ratio
Lactate dehydrogenase |
| Issue Date: | Jun-2010 |
| Publisher: | CSIR |
| Abstract: | Neurons and astrocytes differentially
express isoenzymes of lactate dehydrogenase (LDH). The metabolic consequences
for the variations in mRNA expression of LDH isoenzyme subtypes in neurons and
astrocytes control cerebral vasoregulation. Moreover, cellular signalling
consequences for functional neurovascular control may also be dependent on LDH
isoenzyme subtype profiles. Initial computer simulations revealed
glutamate-induced calcium waves in connected astrocytes, and showed concomitant
changes in the expression of nitric oxide synthase (NOS) and lactic acid
metabolism. To validate these findings, the nature and extent of
glutamate-dependent signalling crosstalk in murine cell lines were investigated
through correlated lactate levels and calcium upregulation. Neuro2A and C8D1A
cells were separately treated with timed supernatant extracts from each other
and their LDH1 and LDH5 isoenzyme responses were recorded. Western blot
analysis showed LDH1/LDH5 isoenzyme ratio in the astrocytes to be positively
correlated with Neuro2A-derived lactate levels estimated by the amplitude of
1.33-ppm spectral peak in 1H-NMR, and LDH1/LDH5 isoenzyme ratio in
neurons is negatively correlated with C8D1A-derived lactate levels. Significant
modulations of the calcium-responsive protein pCamKII levels were also observed
in both cell lines, particularly correlations between pCamKII and lactate in
C8D1A cells, thus explaining the calcium dependence of the lactate response.
Together, these observations indicate that lactate is a key indicator of the
metabolic state of these cell types, and may be a determinant of release of
vasoregulatory factors. |
| Page(s): | 529-537 |
| ISSN: | 0975-1009 (Online); 0019-5189 (Print) |
| Source: | IJEB Vol.48(06) [June 2010]
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