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The Effects of Cholera Toxin on Cellular Energy Metabolism
Department of Chemistry, Vanderbilt University, VU Station B. Nashville, TN 37235-1822, USA
Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37235-1809, USA
Departments of Physics, Biomedical Engineering, and Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37235-1809, USA
* Author to whom correspondence should be addressed.
Received: 11 March 2010; in revised form: 31 March 2010 / Accepted: 6 April 2010 / Published: 8 April 2010
Abstract: Multianalyte microphysiometry, a real-time instrument for simultaneous measurement of metabolic analytes in a microfluidic environment, was used to explore the effects of cholera toxin (CTx). Upon exposure of CTx to PC-12 cells, anaerobic respiration was triggered, measured as increases in acid and lactate production and a decrease in the oxygen uptake. We believe the responses observed are due to a CTx-induced activation of adenylate cyclase, increasing cAMP production and resulting in a switch to anaerobic respiration. Inhibitors (H-89, brefeldin A) and stimulators (forskolin) of cAMP were employed to modulate the CTx-induced cAMP responses. The results of this study show the utility of multianalyte microphysiometry to quantitatively determine the dynamic metabolic effects of toxins and affected pathways.
Keywords: cholera toxin; metabolism; multianalyte; microphysiometry; cyclic AMP; forskolin; PC-12
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Snider, R.M.; McKenzie, J.R.; Kraft, L.; Kozlov, E.; Wikswo, J.P.; Cliffel, D.E. The Effects of Cholera Toxin on Cellular Energy Metabolism. Toxins 2010, 2, 632-648.
Snider RM, McKenzie JR, Kraft L, Kozlov E, Wikswo JP, Cliffel DE. The Effects of Cholera Toxin on Cellular Energy Metabolism. Toxins. 2010; 2(4):632-648.
Snider, Rachel M.; McKenzie, Jennifer R.; Kraft, Lewis; Kozlov, Eugene; Wikswo, John P.; Cliffel, David E. 2010. "The Effects of Cholera Toxin on Cellular Energy Metabolism." Toxins 2, no. 4: 632-648.