Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0917798 (
cerebral ischemia
)
17,036
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The reticulon family has been found to induce apoptosis, inhibit axon regeneration and regulate protein trafficking. However, little is known about the mechanisms of how reticulon proteins are involved in neuronal death-promoting processes during ischemia. Here, we report that the expression of Reticulon Protein 1-C (RTN1-C) was associated with the progression of
cerebral ischemia
/reperfusion (I/R) injury. Using a combination of rat middle cerebral artery occlusion (MCAO) stroke and oxygen-glucose deprivation followed by reoxygenation (OGD/R) models, we determined that the expression of
RTN1
-C was significantly increased during cerebral ischemic/reperfusion.
RTN1
-C overexpression induced apoptosis and increased the cell vulnerability to ischemic injury, whereas
RTN1
-C knockdown reversed ischemia-induced apoptosis and attenuated the vulnerability of OGD/R-treated neural cells. Mechanistically, we demonstrated that
RTN1
-C mediated OGD/R-induced apoptosis through ER stress and mitochondria-associated pathways.
RTN1
-C interacted with Bcl-xL and increased its localization in the ER, thus reducing the anti-apoptotic activity of Bcl-xL. Most importantly, knockdown of Rtn1-c expression in vivo attenuated apoptosis in MCAO rats and reduced the extent of I/R-induced brain injury, as assessed by infarct volume and neurological score. Collectively, these data support for the first time that
RTN1
-C may represent a novel candidate for therapies against
cerebral ischemia
/reperfusion injury.
...
PMID:RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways. 2898 Oct 95
Reticulons (RTNs) are a family of membrane-bound proteins that are dominantly localized to the endoplasmic reticulum (ER) membrane.
RTN1
-C is one member of RTNs abundantly expressed in the brain and has been shown to mediate neuronal injury in
cerebral ischemia
models. In the present study, we investigated the role of
RTN1
-C in an in vitro brain trauma model mimicked by traumatic neuronal injury (TNI) in primary cultured cortical neurons. TNI increased the expression of
RTN1
-C in cortical neurons but had no effect on
RTN1
-A and
RTN1
-B. Knockdown of
RTN1
-C with specific siRNA (Si-
RTN1
-C) significantly decreased cytotoxicity and apoptosis after TNI. The results of Ca
2+
imaging showed that intracellular Ca
2+
overload induced by TNI was attenuated by
RTN1
-C knockdown. Furthermore, the activation of metabotropic glutamate receptor 1 (mGluR1)-induced Ca
2+
response was partially prevented by Si-
RTN1
-C transfection. We also evaluated the role of
RTN1
-C in store-operated Ca
2+
entry (SOCE) in cortical neurons using the ER Ca
2+
inducer thapsigargin (Tg). The results showed that knockdown of
RTN1
-C alleviated the SOCE-mediated Ca
2+
influx and decreased the expression of stromal interactive molecule 1 (STIM1). In summary, the present study found that knockdown of
RTN1
-C protected neurons against TNI via preservation of intracellular Ca
2+
homeostasis, which was associated with the inhibition of mGluR1-mediated ER Ca
2+
release and suppression of STIM1-related SOCE. Thus,
RTN1
-C might represent a therapeutic target for traumatic brain injury (TBI) research.
...
PMID:Knockdown of RTN1-C attenuates traumatic neuronal injury through regulating intracellular Ca
2+
homeostasis. 3035 62
Reticulons (RTNs) are a group of membrane-bound proteins that are dominantly localized to the endoplasmic reticulum (ER).
RTN1
-C, one isoform of RTNs highly expressed in the brain, has been shown to mediate neuronal injury in
cerebral ischemia
models. The aim of this study was to investigate the role of
RTN1
-C in an in vitro model of Parkinson's disease (PD) mimicked by 1-methyl-4-phenylpyridinium (MPP
+
) treatment in SN4741 cells. We found that MPP
+
significantly increased the expression of
RTN1
-C, with no effect on
RTN1
-A and
RTN1
-B. Downregulation of
RTN1
-C using siRNA (Si-
RTN1
-C) markedly increased cell viability and inhibited apoptosis induced by MPP
+
treatment. The results of western blot showed that downregulation of
RTN1
-C inhibited the surface expression of metabotropic glutamate receptor 5 (mGluR5) but had no effect on mGluR1. The protective effects of Si-
RTN1
-C were partially prevented by activating mGluR5, not mGluR1. In addition, the results of Ca
2+
imaging showed that downregulation of
RTN1
-C attenuated intracellular Ca
2+
release induced by MPP
+
, which could be nullified by activation of mGluR5 pathway. In conclusion, our data suggest that downregulation of
RTN1
-C protects SN4741 cells against MPP
+
through mGluR5-mediated preservation of Ca
2+
homeostasis. Therefore,
RTN1
-C might represent a therapeutic target for the treatment of neuronal injury in experimental PD models.
...
PMID:Downregulation of RTN1-C attenuates MPP
+
-induced neuronal injury through inhibition of mGluR5 pathway in SN4741 cells. 3052 40
