Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
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Target Concepts:
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Query: UNIPROT:P51812 (
mitogen-activated protein
)
10,636
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cell death was assessed by quantitative analysis of propidium iodide uptake in rat hippocampal slice cultures transiently exposed to oxygen and glucose deprivation, an in vitro model of brain ischemia. The hippocampal subfields CA1 and CA3, and fascia dentata were analyzed at different stages from 0 to 48 h after the insult. Cell death appeared at 3 h and increased steeply toward 12 h. Only a slight additional increase in propidium iodide uptake was seen at later intervals. The
mitogen-activated protein
kinases extracellular signal-regulated kinase 1 and extracellular signal-regulated kinase 2 were activated immediately after oxygen and glucose deprivation both in CA1 and in CA3/fascia dentata. Inhibition of the specific mitogen-activated protein kinase activator mitogen-activated protein kinase kinase by PD98059 or U0126 offered partial protection against oxygen and glucose deprivation-induced cell damage. The non-selective P2X receptor antagonist suramin gave neuroprotection of the same magnitude as the N-methyl-D-aspartate channel blocker MK-801 (approximately 70%). Neuroprotection was also observed with the P2 receptor blocker
PPADS
. Immunogold data indicated that hippocampal slice cultures (like intact hippocampi) express several isoforms of P2X receptors at the synaptic level, consistent with the idea that the effects of suramin and
PPADS
are mediated by P2X receptors. Virtually complete neuroprotection was obtained by combined blockade of N-methyl-D-aspartate receptors, P2X receptors, and mitogen-activated protein kinase kinase. Both P2X receptors and N-methyl-D-aspartate receptors mediate influx of calcium. Our results suggest that inhibition of P2X receptors has a neuroprotective potential similar to that of inhibition of N-methyl-D-aspartate receptors. In contrast, our comparative analysis shows that only partial protection can be achieved by inhibiting the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase cascade, one of the downstream pathways activated by intracellular calcium overload.
...
PMID:Neuroprotective effects of inhibiting N-methyl-D-aspartate receptors, P2X receptors and the mitogen-activated protein kinase cascade: a quantitative analysis in organotypical hippocampal slice cultures subjected to oxygen and glucose deprivation. 1634 52
We investigated the effects of salt-sensitive signaling molecules on ionic fluxes and gene expression related to K
+
/Na
+
homeostasis in a perennial herb,
Glycyrrhiza uralensis
, during short-term NaCl stress (100 mM, 24 h). Salt treatment caused more pronounced Na
+
accumulation in root cells than in leaf cells. Na
+
ions were mostly compartmentalized in vacuoles. Roots exposed to NaCl showed increased levels of extracellular ATP (eATP), cytosolic Ca
2+
, H
2
O
2
, and NO. Steady-state flux recordings revealed that these salt-sensitive signaling molecules enhanced NaCl-responsive Na
+
efflux, due to the activated Na
+
/H
+
antiport system in the plasma membrane (PM). Moreover, salt-elicited K
+
efflux, which was mediated by depolarization-activated cation channels, was reduced with the addition of Ca
2+
, H
2
O
2
, NO, and eATP. The salt-adaptive effects of these molecules (Na
+
extrusion and K
+
maintenance) were reduced by pharmacological agents, including LaCl
3
(a PM Ca
2+
channel inhibitor), DMTU (a reactive oxygen species scavenger), cPTIO (an NO scavenger), or
PPADS
(an antagonist of animal PM purine P2 receptors). RT-qPCR data showed that the activation of the PM Na
+
/H
+
antiport system in salinized roots most likely resulted from the upregulation of two genes,
GuSOS1
and
GuAHA
, which encoded the PM Na
+
/H
+
antiporter, salt overly sensitive 1 (SOS1), and H
+
-ATPase, respectively. Clear interactions occurred between these salt-sensitive agonists to accelerate transcription of salt-responsive signaling pathway genes in
G. uralensis
roots. For example, Ca
2+
, H
2
O
2
, NO, and eATP promoted transcription of
GuSOS3
(salt overly sensitive 3) and/or
GuCIPK
(CBL-interacting protein kinase) to activate the predominant Ca
2+
-SOS signaling pathway in salinized liquorice roots. eATP, a novel player in the salt response of
G. uralensis
, increased the transcription of
GuSOS3, GuCIPK
,
GuRbohD
(respiratory burst oxidase homolog protein D),
GuNIR
(nitrate reductase),
GuMAPK3
, and
GuMAPK6
(the
mitogen-activated protein
kinases 3 and 6). Moreover,
GuMAPK3
and
GuMAPK6
expression levels were enhanced by H
2
O
2
in NaCl-stressed
G. uralensis
roots. Our results indicated that eATP triggered downstream components and interacted with Ca
2+
, H
2
O
2
, and NO signaling to maintain K
+
/Na
+
homeostasis. We propose that a multiple signaling network regulated K
+
/Na
+
homeostasis in NaCl-stressed
G. uralensis
roots.
...
PMID:Salt-Sensitive Signaling Networks in the Mediation of K
+
/Na
+
Homeostasis Gene Expression in
Glycyrrhiza uralensis
Roots. 2885 12
