Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptosis of arterial cells induced by oxidized low density lipoproteins (OxLDL) is thought to contribute to the progression of atherosclerosis. However, most data on apoptotic effects and mechanisms of OxLDL were obtained with extensively oxidized LDL unlikely to occur in early stages of atherosclerotic lesions. We now demonstrate that mildly oxidized LDL generated by incubation with oxygen radical-producing xanthine/xanthine oxidase (X/XO) induces apoptosis in primary cultures of human coronary endothelial and SMC, as determined by TUNEL technique, DNA laddering, and FACS analysis. Apoptosis was markedly reduced when X/XO-LDL was generated in the presence of different oxygen radical scavengers. Apoptotic signals were mediated by intramembrane domains of both Fas and tumor necrosis factor (TNF) receptors I and II. Blocking of Fas ligand (FasL) reduced apoptosis by 50% and simultaneous blocking of FasL and TNF receptors by 70%. Activation of apoptotic receptors was accompanied by an increase of proapoptotic and a decrease in antiapoptotic proteins of the Bcl-2 family and resulted in marked activation of class I and II caspases. Mildly oxidized LDL also activated MAP and Jun kinases and increased p53 and other transcription factors (ATF-2, ELK-1, CREB, AP-1). Inhibitors of Map and Jun kinase significantly reduced apoptosis. Our results provide the first evidence that OxLDL-induced apoptosis involves TNF receptors and Jun activation. More important, they demonstrate that even mildly oxidized LDL formed in atherosclerotic lesions may activate a broad cascade of oxygen radical-sensitive signaling pathways affecting apoptosis and other processes influencing the evolution of plaques. Thus, we suggest that extensive oxidative modifications of LDL are not necessary to influence signal transduction and transcription in vivo.
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PMID:Mildly oxidized low density lipoprotein activates multiple apoptotic signaling pathways in human coronary cells. 1102 84

With the Western-blot analysis, we studied the activation of MAP/ERK protein kinases (regulating genes expression by the phosphorylation of transcription factors (TF) CREB and ELK-1) in native Helix pomatia and in animals with disturbed abilities to form long-term conditioned avoidance reflexes. Different stages of this reflex formation were shown to be characterized by different levels of MAP/ERK kinases activation, the latter being different in CNS's regions (visceral complex of ganglia, cerebral and pedal ganglia) playing different roles in the reflex formation. The dynamics of activation was wave-shaped with peaks at 10 min and 4 h. The treatment of snails with the neurotoxin 5,7-DHT (causing disfunction of serotoninergic terminals and reducing capability for this reflex formation) resulted in significant decrease of MAP/ERK kinase cascade activation at earlier stages of learning, which suggest an important role of serotoninergic system in this cascade activation. The activation of MAP/ERK kinase cascade in 4 hours after training was observed in native as well as in DHT-treated animals, which seems to suggest, switching on nonspecific adaptive processes in response to sensitizing unconditioned stimulus. Thus, MAP/ERK kinase intracellular regulatory cascade playing an important role in neuron survival, processes regeneration and synaptic sprouting plays an important role in the formation of serotonin-dependent food aversion reflex in Helix pomatia.
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PMID:[Comparative analysis of MAP/ERK-kinase activation in the CNS of animals with different capability for learning]. 1686 82

Western blot analysis was used to study the activation of MAP/ERK protein kinases responsible for controlling gene expression via phosphorylation of transcription factors CREB and ELK-1 in native common snails and animals with impaired abilities to form long-term types of conditioned aversive reflexes. Different periods of the formation of this reflex were found to be characterized by different levels of activation of MAP-ERK kinases. The extents of activation of MAP-ERK kinase cascade were different in ganglia (parietal-visceral, cerebral, and pedal) with different roles in the formation of this reflex. The dynamics of activation showed a wavelike nature, with peaks at 10 min and 4 h. Administration of the neurotoxin 5,7-DHT, which induces dysfunction of serotonin terminals and decreases the ability to acquire this type of learning, led to significant decreases in activation of the MAP-ERK kinase cascade at the early stages of learning, which is evidence for an important role for the serotoninergic system in inducing this cascade. Activation of the MAP/ERK kinase cascade 4 h after training was seen both in native and DHT-treated animals, which is probably evidence for activation of non-specific adaptive processes in response to the sensitizing unconditioned stimulus. Thus, the MAP/ERK kinase intracellular regulatory cascade, which plays an important role in the survival of neurons, the regeneration of neuron processes, and synaptic sprouting, also plays an important role in forming the serotonin-dependent food-aversive reflex in the common snail.
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PMID:Comparative analysis of the activation of MAP/ERK kinases in the CNS of animals with different learning abilities. 1776 91