Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glutamate neurotoxicity is one of the causative factors leading to neural degeneration including retina. Inhibition of NMDA receptors has been shown neuroprotective effects. However, specifically inhibition of glycine subunit in NMDA receptors and its effects on retina neural protection has not been tested. In this study, using a glycine site-specific NMDA receptor antagonist, we investigated its neuroprotective effects on rat retinal ganglion cells (RGCs) from a transient ischemic injury and its possible underlying mechanisms. Following an ischemia/reperfusion injury the structural damages of rat retinas were assessed by an immunofluorescence method and the apoptosis of retinal neural cells was evaluated by using a terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method. The survived RGCs were labeled by retrograde manner and counted on whole-mounted retinas. In the presence of glycine site-specific NMDA receptor antagonist, the thickness of retina was sustained, especially in the inner nuclear layers compared with mock controls. While a significantly higher numbers of TUNEL-positive apoptotic cells and fewer of RGCs were observed in the retina without the glycine antagonist, indicating its strong protective roles. Some apoptotic factors such as Bax, Bcl-2, CAMK II, COX1, COX4, Caspase-3, and GRIN1 gene have been tested from retinal samples with or without the glycine antagonist. A significantly lower of expressions of Bax, CAMK II, COX1, COX4, Caspase-3, and GRIN1 have been shown in the retinas with the antagonist. Bcl-2/Bax ratio was significantly higher with the antagonist, suggested that the glycine site-specific NMDA receptor antagonist protecting RGC death might through inhibition of apoptotic signaling.
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PMID:A glycine site-specific NMDA receptor antagonist protects retina ganglion cells from ischemic injury by modulating apoptotic cascades. 2033 77

This study investigated the effects of fluoride exposure on the mRNA expression of Cav1.2 calcium signaling pathway and apoptosis regulatory molecules in PC12 cells. The viability of PC12 cell receiving high fluoride (5.0mM) and low fluoride (0.5mM) alone or fluoride combined with L-type calcium channel (LTCC) agonist/inhibitor (5umol/L FPL6417/2umol/L nifedipine) was detected using cell counting kit-8 at different time points (2, 4, 6, 8, 12, 10, and 24h). Changes in the cell configuration were observed after exposing the cells to fluoride for 24h. The expression levels of molecules related to the LTCC were examined, particularly, Cav1.2, c-fos, CAMK II, Bax, and Bcl-2. Fluoride poisoning induced severe cell injuries, such as decreased PC12 cell activity, enhanced cell apoptosis, high c-fos, CAMKII, and Bax mRNA expression levels. Bcl-2 expression level was also reduced. Meanwhile, high fluoride, high fluoride with FPL64176, and low fluoride with FPL64176 enhanced the Cav1.2 expression level. In contrast, low fluoride, high fluoride with nifedipine, and low fluoride with nifedipine reduced the Cav1.2 expression level. Thus, Cav1.2 may be an important molecular target for the fluorosis treatment, and the LTCC inhibitor nifedipine may be an effective drug for fluorosis.
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PMID:Effect of fluoride exposure on mRNA expression of cav1.2 and calcium signal pathway apoptosis regulators in PC12 cells. 2869 52