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AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha and nuclear respiratory factor 1 expression in rat visual cortical neurons.
Neuroscience. 2010 Aug 11; 169(1):23-38.N

Abstract

Nuclear respiratory factor 1 (NRF-1) is one of the key transcription factors implicated in mitochondrial biogenesis by activating the transcription of mitochondrial transcription factor A (mtTFA) and subunit genes of respiratory enzymes. NRF-1 transactivation activity can be enhanced by interaction with transcription coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha). The expression of PGC-1alpha, NRF-1 and mtTFA in neurons is known to be tightly regulated by neuronal activity. However, the coupling signaling mechanism is poorly understood. Here, we use primary cultures of rat visual cortical neurons and a rat model of monocular deprivation (MD) to investigate whether AMP-activated protein kinase (AMPK) is implicated in mediating activity-dependent regulation of PGC-1alpha and NRF-1 expression in neurons. We find that KCl depolarization rapidly activates AMPK and significantly increases PGC-1alpha, NRF-1, and mtTFA levels with increased ATP production in neuron cultures. Similarly, pharmacological activation of AMPK with 5'-aminoimidazole-4-carboxamide riboside (AICAR) or resveratrol also markedly increases PGC-1alpha and NRF-1 mRNA levels in neuron cultures. All these effects can be completely blocked by an AMPK inhibitor, Compound C. Conversely, 1 week of MD significantly reduces AMPK phosphorylation and activity, dramatically down-regulates PGC-1alpha and NRF-1 expression in deprived primary visual cortex. Administration of resveratrol in vivo significantly activates AMPK activity and attenuates the effects of MD on mitochondria by significant increase in PGC-1alpha and NRF-1 levels, mitochondria amount, and coupled respiration. These results strongly indicate that AMPK is an essential upstream mediator that couples neuronal activity to mitochondrial energy metabolism by regulation of PGC-1alpha-NRF-1 pathway in neurons.

Authors+Show Affiliations

Department of Pathology, Xi Jing Hospital, 4th Military Medical University, Xi'an, Shaanxi 710032, PR China.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20438809

Citation

Yu, L, and S J. Yang. "AMP-activated Protein Kinase Mediates Activity-dependent Regulation of Peroxisome Proliferator-activated Receptor Gamma Coactivator-1alpha and Nuclear Respiratory Factor 1 Expression in Rat Visual Cortical Neurons." Neuroscience, vol. 169, no. 1, 2010, pp. 23-38.
Yu L, Yang SJ. AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha and nuclear respiratory factor 1 expression in rat visual cortical neurons. Neuroscience. 2010;169(1):23-38.
Yu, L., & Yang, S. J. (2010). AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha and nuclear respiratory factor 1 expression in rat visual cortical neurons. Neuroscience, 169(1), 23-38. https://doi.org/10.1016/j.neuroscience.2010.04.063
Yu L, Yang SJ. AMP-activated Protein Kinase Mediates Activity-dependent Regulation of Peroxisome Proliferator-activated Receptor Gamma Coactivator-1alpha and Nuclear Respiratory Factor 1 Expression in Rat Visual Cortical Neurons. Neuroscience. 2010 Aug 11;169(1):23-38. PubMed PMID: 20438809.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - AMP-activated protein kinase mediates activity-dependent regulation of peroxisome proliferator-activated receptor gamma coactivator-1alpha and nuclear respiratory factor 1 expression in rat visual cortical neurons. AU - Yu,L, AU - Yang,S J, Y1 - 2010/05/18/ PY - 2009/12/19/received PY - 2010/04/23/revised PY - 2010/04/25/accepted PY - 2010/5/5/entrez PY - 2010/5/5/pubmed PY - 2011/3/5/medline SP - 23 EP - 38 JF - Neuroscience JO - Neuroscience VL - 169 IS - 1 N2 - Nuclear respiratory factor 1 (NRF-1) is one of the key transcription factors implicated in mitochondrial biogenesis by activating the transcription of mitochondrial transcription factor A (mtTFA) and subunit genes of respiratory enzymes. NRF-1 transactivation activity can be enhanced by interaction with transcription coactivator peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha). The expression of PGC-1alpha, NRF-1 and mtTFA in neurons is known to be tightly regulated by neuronal activity. However, the coupling signaling mechanism is poorly understood. Here, we use primary cultures of rat visual cortical neurons and a rat model of monocular deprivation (MD) to investigate whether AMP-activated protein kinase (AMPK) is implicated in mediating activity-dependent regulation of PGC-1alpha and NRF-1 expression in neurons. We find that KCl depolarization rapidly activates AMPK and significantly increases PGC-1alpha, NRF-1, and mtTFA levels with increased ATP production in neuron cultures. Similarly, pharmacological activation of AMPK with 5'-aminoimidazole-4-carboxamide riboside (AICAR) or resveratrol also markedly increases PGC-1alpha and NRF-1 mRNA levels in neuron cultures. All these effects can be completely blocked by an AMPK inhibitor, Compound C. Conversely, 1 week of MD significantly reduces AMPK phosphorylation and activity, dramatically down-regulates PGC-1alpha and NRF-1 expression in deprived primary visual cortex. Administration of resveratrol in vivo significantly activates AMPK activity and attenuates the effects of MD on mitochondria by significant increase in PGC-1alpha and NRF-1 levels, mitochondria amount, and coupled respiration. These results strongly indicate that AMPK is an essential upstream mediator that couples neuronal activity to mitochondrial energy metabolism by regulation of PGC-1alpha-NRF-1 pathway in neurons. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/20438809/AMP_activated_protein_kinase_mediates_activity_dependent_regulation_of_peroxisome_proliferator_activated_receptor_gamma_coactivator_1alpha_and_nuclear_respiratory_factor_1_expression_in_rat_visual_cortical_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(10)00630-5 DB - PRIME DP - Unbound Medicine ER -