Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.31 (AMP-activated protein kinase)
 13,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Traumatic brain injury (TBI) produces a state of vulnerability that reduces the brain capacity to cope with secondary insults. The silent information regulator 2 (Sir2) has been implicated with maintaining genomic stability and cellular homeostasis under challenging situation. Here we explore the possibility that the action of Sir2alpha (mammalian Sir2) in the brain can extend to serve neuronal plasticity. We provide novel evidence showing that mild TBI reduces the expression of Sir2alpha in the hippocampus, in proportion to increased levels of protein oxidation. In addition, we show that dietary supplementation of omega-3 fatty acids that ameliorates protein oxidation was effective to reverse the reduction of Sir2alpha level in injured rats. Given that oxidative stress is a subproduct of dysfunctional energy homeostasis, we measured AMP-activated protein kinase (AMPK) and phosphorylated-AMPK (p-AMPK) to have an indication of the energy status of cells. Hippocampal levels of total and phosphorylated AMPK were reduced after TBI and levels were normalized by omega-3 fatty acts supplements. Further, we found that TBI reduced ubiquitous mitochondrial creatine kinase (uMtCK), an enzyme implicated in the energetic regulation of Ca2+-pumps and in the maintenance of Ca2+-homeostasis. Omega-3 fatty acids supplements normalized the levels of uMtCK after lesion. Furthermore, we found that the correlation between Sir2alpha and AMPK or p-AMPK was disrupted by TBI, but restored by omega-3 fatty acids supplements. Our results suggest that TBI may compromise neuronal protective mechanisms by involving the action of Sir2alpha. In addition, results show the capacity of omega-3 fatty acids to counteract some of the effects of TBI by normalizing levels of molecular systems associated with energy homeostasis.
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PMID:Omega-3 fatty acids supplementation restores mechanisms that maintain brain homeostasis in traumatic brain injury. 1797 Jun 22

Brain-derived neurotrophic factor (BDNF) has been shown to mediate the effects of exercise on synaptic plasticity and cognitive function, in a process in which energy metabolism probably plays an important role. The purpose of the present study was to examine the influence of exercise on rat hippocampal expression of molecules involved in the regulation of energy management and cognitive function, and to determine the role of BDNF in these events. One week of voluntary exercise that enhanced learning and memory performance elevated the expression of molecular systems involved in the metabolism of energy [AMP-activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and uncoupling protein 2] and molecules that work at the interface of energy and synaptic plasticity [BDNF, insulin-like growth factor I (IGF-I) and ghrelin]. The levels of BDNF mRNA were associated with the mRNA levels of AMPK, uMtCK, IGF-I and ghrelin. Inhibiting the action of BDNF during exercise abolished an exercise-mediated enhancement in spatial learning and increased the expression of all of the molecular systems studied. BDNF blocking also disrupted the association between learning speed and levels of AMPK, uMtCK, ghrelin and IGF-I mRNAs. These findings suggest that the effects of exercise on synaptic plasticity and cognitive function involve elements of energy metabolism, and that BDNF seems to work at the interface between the two processes as a metabotrophin.
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PMID:Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. 1904 71

Traumatic brain injury (TBI) is followed by an energy crisis that compromises the capacity of the brain to cope with challenges, and often reduces cognitive ability. New research indicates that events that regulate energy homeostasis crucially impact synaptic function and this can compromise the capacity of the brain to respond to challenges during the acute and chronic phases of TBI. The goal of the present study is to determine the influence of the phenolic yellow curry pigment curcumin on molecular systems involved with the monitoring, balance, and transduction of cellular energy, in the hippocampus of animals exposed to mild fluid percussion injury (FPI). Young adult rats were exposed to a regular diet (RD) without or with 500 ppm curcumin (Cur) for four weeks, before an FPI was performed. The rats were assigned to four groups: RD/Sham, Cur/Sham, RD/FPI, and Cur/FPI. We found that FPI decreased the levels of AMP-activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and cytochrome c oxidase II (COX-II) in RD/FPI rats as compared to the RD/sham rats. The curcumin diet counteracted the effects of FPI and elevated the levels of AMPK, uMtCK, COX-II in Cur/FPI rats as compared to RD/sham rats. In addition, in the Cur/sham rats, AMPK and uMtCK increased compared to the RD/sham. Results show the potential of curcumin to regulate molecules involved in energy homeostasis following TBI. These studies may foster a new line of therapeutic treatments for TBI patients by endogenous upregulation of molecules important for functional recovery.
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PMID:Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma. 1939 1