Understanding the mechanism of control of energy metabolism is central to understanding cellular homeostasis. Defects in energy metabolism are associated with a number of disease states. The major objective of this project is to combine NMR and transgenic mice techniques to study cellular energy metabolism in the liver, muscle, heart and brain. Recent 31P-NMR results in heart have shown that with increased work and oxygen consumption, there are no changes in levels of inorganic phosphate (Pi), phosphocreatine (PCr), or ATP. In addition, there are no changes in the calculated pH, [Mg2+], or [ADP]. These results call into question the widely held view that alterations in these metabolites couple increases in ATPase activity to increases in mitochondrial ATP production rates. We are interested in analyzing the regulation of mitochondrial ATP production in liver, muscle, and brain using NMR and transgenic mouse techniques. We have begun this research by manipulating creatine kinase activity. We have begun to manipulate the creatine kinase level and isoform distribution in a variety of mouse tissues to help elucidate the control of energy metabolism. Over the past few years, we have been analyzing transgenic mice that express the B isozyme of creatine kinase in liver using 31p NMR. In addition, we have succeeded in altering the creatine kinase isozyme distribution in muscle by overexpression of the B subunit and have continued the analysis of these mice. This line, in combination with a recently produced line of mice missing the normal muscle MM creatine kinase, has allowed us to produce a line of mice with a complete isoenzyme switch from MM to BB creatine kinase. We have also produced and begun to characterize a line of transgenic mice expressing the mitochondrial form of creatine kinase in liver. Finally, we have produced transgenic mice expressing myoglobin in brain to investigate the role of oxygen delivery in cellular energy metabolism.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
2P41RR003631-11
Application #
6121736
Study Section
Project Start
1998-09-15
Project End
1999-08-14
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Carnegie-Mellon University
Department
Type
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Ramachandran, Suchitra; Meyer, Travis; Olson, Carl R (2016) Prediction suppression in monkey inferotemporal cortex depends on the conditional probability between images. J Neurophysiol 115:355-62
Meyer, Travis; Walker, Christopher; Cho, Raymond Y et al. (2014) Image familiarization sharpens response dynamics of neurons in inferotemporal cortex. Nat Neurosci 17:1388-94
Hall, Nathan; Colby, Carol (2014) S-cone visual stimuli activate superior colliculus neurons in old world monkeys: implications for understanding blindsight. J Cogn Neurosci 26:1234-56
Subramanian, Janani; Colby, Carol L (2014) Shape selectivity and remapping in dorsal stream visual area LIP. J Neurophysiol 111:613-27
Berdyyeva, Tamara K; Olson, Carl R (2014) Intracortical microstimulation of supplementary eye field impairs ability of monkeys to make serially ordered saccades. J Neurophysiol 111:1529-40
Meyer, Travis; Ramachandran, Suchitra; Olson, Carl R (2014) Statistical learning of serial visual transitions by neurons in monkey inferotemporal cortex. J Neurosci 34:9332-7
Hall, Nathan; Colby, Carol (2013) Psychophysical definition of S-cone stimuli in the macaque. J Vis 13:
Leathers, Marvin L; Olson, Carl R (2012) In monkeys making value-based decisions, LIP neurons encode cue salience and not action value. Science 338:132-5
Meyer, Travis; Olson, Carl R (2011) Statistical learning of visual transitions in monkey inferotemporal cortex. Proc Natl Acad Sci U S A 108:19401-6
Berdyyeva, Tamara K; Olson, Carl R (2011) Relation of ordinal position signals to the expectation of reward and passage of time in four areas of the macaque frontal cortex. J Neurophysiol 105:2547-59

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