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Proteomic profiling of the phosphoproteins in the rat thalamus, hippocampus and frontal lobe after propofol anesthesia.

ABSTRACT: BACKGROUND: Propofol is a safe and effective intravenous anesthetic that is widely used for the induction and maintenance of anesthesia during surgery. However, the mechanism by which propofol exerts its anesthetic effect remains unknown. The rapid onset of phosphorylation modifications coincides with that of propofol anesthesia. METHODS: Propofol-anesthetized rat models were built and phosphorylated proteins in the thalamus, hippocampus and frontal lobe were enriched the to analyze the changes in these phosphoproteins after propofol anesthesia. RESULTS: Sixteen of these phosphoprotein spots were successfully identified using MALDI-TOF MS and a subsequent comparative sequence search in the Mascot database. Of these proteins, keratin 18 and the tubulin 2c chain are cytoskeletal proteins; keratin 18 and gelsolin are relevant to alcohol drowsiness. Based on Western blot analysis, we also confirmed that the phosphorylation of these proteins is directly induced by propofol, indicating that propofol anesthesia may be relevant to cytoskeletal proteins and alcohol drowsiness. CONCLUSIONS: These identified propofol-induced phosphorylations of proteins provide meaningful contributions for further studying the anesthetic mechanism of propofol.

SUBMITTER: Tang J

PROVIDER: S-EPMC3922749 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Proteomic profiling of the phosphoproteins in the rat thalamus, hippocampus and frontal lobe after propofol anesthesia.

Tang Jing J Xue Qiong Q Ding Hong H Qin Zaisheng Z Xiao Jinfang J Lin Chunshui C Liu Youtan Y Tao Tao T

BMC anesthesiology 20140110

<h4>Background</h4>Propofol is a safe and effective intravenous anesthetic that is widely used for the induction and maintenance of anesthesia during surgery. However, the mechanism by which propofol exerts its anesthetic effect remains unknown. The rapid onset of phosphorylation modifications coincides with that of propofol anesthesia.<h4>Methods</h4>Propofol-anesthetized rat models were built and phosphorylated proteins in the thalamus, hippocampus and frontal lobe were enriched the to analyze ...[more]

PMID: 24410762

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Project description:BackgroundTo identify the biochemical changes induced by sleep deprivation at a proteomic level, we compared the hippocampal proteome of rats either after 4 hours of sleep or sleep deprivation obtained by gentle handling. Because sleep deprivation might induce some stress, we also analyzed proteomic changes in rat adrenals in the same conditions. After sleep deprivation, proteins from both tissues were extracted and subjected to 2D-DIGE analysis followed by protein identification through mass spectrometry and database search.ResultsIn the hippocampus, 87 spots showed significant variation between sleep and sleep deprivation, with more proteins showing higher abundance in the latter case. Of these, 16 proteins were present in sufficient amount for a sequencing attempt and among the 12 identified proteins, inferred affected cellular functions include cell metabolism, energy pathways, transport and vesicle trafficking, cytoskeleton and protein processing. Although we did not observe classical, macroscopic effect of stress in sleep-deprived rats, 47 protein spots showed significant variation in adrenal tissue between sleep and sleep deprivation, with more proteins showing higher abundance following sleep. Of these, 16 proteins were also present in sufficient amount for a sequencing attempt and among the 13 identified proteins, the most relevant cellular function that was affected was cell metabolism.ConclusionAt a proteomic level, short term sleep deprivation is characterized by a higher expression of some proteins in the hippocampus and a lower abundance of other proteins in the adrenals (compared to normal sleep control). Altogether, this could indicate a general activation of a number of cellular mechanisms involved in the maintenance of wakefulness and in increased energy expenditure during sleep deprivation. These findings are relevant to suggested functions of sleep like energy repletion and the restoration of molecular stocks or a more global homeostasis of synaptic processes.

Project description:BackgroundAlthough controversial, experimental data suggest the use of propofol may be associated with neurotoxicity. The mechanisms responsible for propofol neurotoxicity in animals are not yet clear.ObjectiveThis study aimed to determine the effects of propofol on the proliferation of neural stem cells in rat hippocampus and the mechanisms underlying these effects.MethodsForty-five adult male Sprague-Dawley rats were randomly divided into 5 groups: Control (N group), intralipid (V group), 30 mg/kg propofol (Prop30 group), 60 mg/kg propofol (Prop60 group), and 120 mg/kg propofol (Prop120 group). The rats in all groups received 5, once daily intraperitoneal injections. For each of the 5 days, the N group received 6 mL/kg normal saline, the V group received 6 mL/kg fat emulsion, the Prop30 group received 30 mg/kg propofol, the Prop60 group received 60 mg/kg propofol, and the Prop120 group received 120 mg/kg propofol. Memory function was scored daily using the Morris water maze test. Immunofluorescence staining was used to histologically monitor the proliferation and differentiation of the rats' hippocampal neural stem cells, and real time quantitative polymerase chain reaction and Western blotting were used to determine the expression of Notch3, Hes1, and Hes5.ResultsCompared with the N group, the Prop120 group exhibited reduced learning and memory, whereas there were no significant differences for the Prop60 group. The number of β-tubulin III+ cells increased in the Prop60 group, but decreased in the Prop120 group. Compared with the N group, the relative expression of Notch3 and Hes5 increased significantly in the Prop60 group, whereas this expression decreased in the Prop120 group.ConclusionsThese data demonstrate that repeated, subchronic (5 days) intraperitoneal injections of 60 mg/kg propofol can effectively promote rat hippocampal neural stem cells proliferation and differentiation, and that this is likely mediated by its effects on the Notch3-Hes5 pathway.

Dataset Information

Proteomic profiling of the phosphoproteins in the rat thalamus, hippocampus and frontal lobe after propofol anesthesia.

Publications

Proteomic profiling of the phosphoproteins in the rat thalamus, hippocampus and frontal lobe after propofol anesthesia.

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