Reticulon Protein-1C: A New Hope in the Treatment of Different Neuronal Diseases

Sano, Federica Di; Piacentini, Mauro

doi:10.1155/2012/651805

Cited by 9 publications

(9 citation statements)

References 85 publications

(117 reference statements)

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“…Previous studies suggested that RTN1 might be involved in the pathogenesis of human diseases, principally neurodegenerative disorders. 21 , 23 , 26 To determine whether RTN1 is involved in cerebral ischemia/reperfusion (I/R) injury, we performed western blot to detect the expressions of the three splice variants of RTN1 in the brain tissue samples of MCAO rats. Among the three splice variants of RTN1, only RTN1-C staining was significantly upregulated by ischemia/reperfusion in rat brains ( Figure 1a ).…”

Section: Resultsmentioning

confidence: 99%

“… 20 Notably, the reticulon family gene 1 (RTN1) was characterized by antibodies that stained a subset of neuroendocrine tissues and was formerly called neuroendocrine specific protein. 21 The RTN1 family has three variants, namely, RTN1-A, RTN1-B and RTN1-C. 22 It has been reported that RTN1-A is a novel mediator of chronic kidney disease progression that promotes renal injury through ER stress. 23 In addition, human RTN1-A and RTN1-B, but not RTN1-C, were found to bind with AP50, a component of the AP-2 adaptor complex that mediates endocytosis.…”

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confidence: 99%

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RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways

et al. 2017

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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.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways

et al. 2017

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“…ER, has been implicated in the pathogenesis of various diseases by interfering with calcium homeostasis and autophagy, resulting in ER stress mediated cell death(Di Sano & Piacentini, 2012; …”

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confidence: 99%

Differential proteomic profiling identifies novel molecular targets of pterostilbene against experimental diabetes

Sireesh

Thiruppathi

Rajaguru

et al. 2018

Journal Cellular Physiology

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Pterostilbene (PTS), a naturally occurring stilbene, confers protection against oxidative and cytokine stress induced pancreatic β-cell apoptosis in vitro and in vivo. To provide insights into the molecular mechanism, we performed a proteomic study on the pancreas of PTS-treated diabetic mice using electrospray ionization tandem-mass spectrometry (LC-MS/MS). A total of 1,260 proteins were detected in triplicate samples. Of which, 359 proteins were found to be differentially regulated in streptozotocin-induced diabetic mice pancreas with two fold difference ( P < 0.05, two or more peptides) and on PTS treatment 315 proteins were normalized to control levels. Gene ontology (GO) indicated that majority of the differentially regulated proteins are involved in cellular functions such as metabolism, cellular structure, oxidative stress, endoplasmic-reticulum-associated protein degradation (ERAD) pathway and several stress sensors. Protein-protein interaction network analysis of these differentially expressed proteins showed clustering of proteins involved in protein processing in endoplasmic reticulum (protein synthesis machinery and protein folding), oxidative phosphorylation/oxidative stress proteins, oligosaccharide metabolic process, and antioxidant activity. Our results highlighted that PTS administration rehabilitated the defective metabolic process and redox imbalance, and also suppressed the unfolded protein response and ERAD pathways. The effects on targeting ER machinery and suppressing oxidative stress suggest the great potential of PTS for diabetes management.

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“…In contrast to the highly conserved C-terminal RHD, the N-terminal regions of RTNs display no sequence similarity at all, even among paralogs within the same species [16]. There is growing evidence showing that RTNs are a group of membrane proteins localized in ER and known to regulate the structure and function of ER [12]. Furthermore, the expression patterns of RTNs and their splice isoforms can be variable, even within the same organism [10,17,18].…”

Section: Discussionmentioning

confidence: 99%

“…Such evidence is particularly pertinent for the RTN1-C [11][12][13]. RTN1-C protein is a membrane protein localized in the ER and expressed in the nervous system, and its function is far from clear [14].…”

Section: Introductionmentioning

confidence: 99%

Identification of MANF as a protein interacting with RTN1-C

Chen¹,

Wan²,

Du³

et al. 2015

ABBS

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Reticulons (RTNs) constitute a family of endoplasmic reticulum (ER)-associated proteins with a reticular distribution. Recently, evidence has shown that they exert a cancer-specific proapoptotic function via interaction or modulation of specific proteins. Such evidence is particularly associated with the RTN1-C family members. In order to explore proteins that interact with RTN1-C, the yeast two-hybrid system and regular molecular biological techniques were used to screen the human fetal brain cDNA library. As a result, seven RTN1-C interacting proteins including Homo sapiens mesencephalic astrocyte-derived neurotrophic factor (MANF) were obtained. The interactions between RTN1-C and its interacting proteins were confirmed by β-galactosidase assay and growth test in selective media. Moreover, the MANF/RTN1-C interaction was verified in vitro by glutathione S-transferase pull-down assay and in vivo by immunoprecipitation assay. By immunofluorescence assay, it was found that MANF co-localized with RTN1-C in the ER. Knockdown of RTN1-C reduced the localization of MANF in the ER. These results provide clues to further explore the function of RTN1-C and MANF in neurodegenerative diseases and cancer.

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Reticulon Protein-1C: A New Hope in the Treatment of Different Neuronal Diseases

Cited by 9 publications

References 85 publications

RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways

RTN1-C mediates cerebral ischemia/reperfusion injury via ER stress and mitochondria-associated apoptosis pathways

Differential proteomic profiling identifies novel molecular targets of pterostilbene against experimental diabetes

Identification of MANF as a protein interacting with RTN1-C

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