Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurodegeneration is a characteristic feature of AIDS dementia complex and is commonly associated with neuronal death in the brains of both pediatric and adult patients. Neuronal death associated with AIDS dementia complex can be induced by the HIV-1 protein gp120, but the underlying signal transduction mechanism remains unclear, especially for HIV-1 subtypes commonly seen in China. We have now demonstrated that the human CC ligand 3-like protein 1 (CCL3L1), a member of the CC chemokine family, appears to protect neuronal cultures through its ability to attenuate gp120-induced neuronal death. We found that (i) both pCREB levels and Bcl-2 expression are up-regulated in neuronal culture following treatment with CCL3L1 plus gp120; (ii) CCL3L1 induces cell survival via phosphorylation of CREB by way of the PKA and CaMKI/CaMKIV cell signaling pathways; (iii) transcription of the cell survival gene bcl-2 is induced by pCREB; and (iv) CCL3L1 protects cultured neurons against CCR5-mediated excitotoxicity induced by gp120. Thus, the CCL3L1/bcl-2-regulated anti-apoptotic pathway significantly contributes to reduction of HIV-1/gp120-induced neuronal apoptosis, and therefore, CCL3L1 should be further investigated as a potential chemokine to protect against neuronal injury in gp120-related neuronal toxicity.
 ...
PMID:CCL3L1 prevents gp120-induced neuron death via the CREB cell signaling pathway. 1910 Jul 22

Previous research demonstrated that glutamate induces neuronal injury partially by increasing intracellular Ca(2+) concentrations ([Ca(2+)]i), and inducing oxidative stress, leading to a neurodegenerative disorder. However, the mechanism of glutamate-induced injury remains elusive. Gastrodin, a major active component of the traditional herbal agent Gastrodia elata (GE) Blume, has been recognized as a potential neuroprotective drug. In the current study, a classical injury model based on glutamate-induced cell death of rat pheochromocytoma (PC12) cells was used to investigate the neuroprotective effect of gastrodin, and its potential mechanisms involved. In this paper, the presence of gastrodin inhibits glutamate-induced oxidative stress as measured by the formation of reactive oxygen species (ROS), the level of malondialdehyde (MDA), mitochondrial membrane potential (MMP), and superoxide dismutase (SOD); gastrodin also prevents glutamate-induced [Ca(2+)]i influx, blocks the activation of the calmodulin-dependent kinase II (CaMKII) and the apoptosis signaling-regulating kinase-1 (ASK-1), inhibits phosphorylation of p38 mitogen-activated kinase (MAPK). Additionally, gastrodin blocked the expression of p53 phosphorylation, caspase-3 and cytochrome C, reduced bax/bcl-2 ratio induced by glutamate in PC12 cells. All these findings indicate that gastrodin protects PC12 cells from the apoptosis induced by glutamate through a new mechanism of the CaMKII/ASK-1/p38 MAPK/p53-signaling pathway.
 ...
PMID:Gastrodin inhibits glutamate-induced apoptosis of PC12 cells via inhibition of CaMKII/ASK-1/p38 MAPK/p53 signaling cascade. 2461 7