RGD Reference Report - Light-Induced Lipocalin 2 Facilitates Cellular Apoptosis by Positively Regulating Reactive Oxygen Species/Bim Signaling in Retinal Degeneration. - Rat Genome Database

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Light-Induced Lipocalin 2 Facilitates Cellular Apoptosis by Positively Regulating Reactive Oxygen Species/Bim Signaling in Retinal Degeneration.

Authors: Tang, Wenyi  Ma, Jun  Gu, Ruiping  Lei, Boya  Ding, Xinyi  Xu, Gezhi 
Citation: Tang W, etal., Invest Ophthalmol Vis Sci. 2018 Dec 3;59(15):6014-6025. doi: 10.1167/iovs.18-25213.
RGD ID: 126781752
Pubmed: PMID:30574656   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.18-25213   (Journal Full-text)


Purpose: Lipocalin 2 (LCN2) is reported to be one of the key regulators of cell survival and death; however, its effect on retinal degeneration is unclear. Therefore, we aimed to investigate the role of LCN2 and its underlying mechanisms in light-induced retinal degeneration.
Methods: A recombinant lentivirus expressing a short hairpin RNA targeting LCN2 mRNA and a recombinant lentivirus overexpressing LCN2 were used to downregulate and upregulate retinal LCN2, respectively. Seven days after intravitreal injection of the lentiviruses, rats were exposed to blue light (2500 lux) for 24 hours. Retinal function and morphology were evaluated with ERG and hematoxylin-eosin staining, respectively. TUNEL staining was used to detect apoptotic cells. The levels of reactive oxygen species (ROS) were evaluated with dihydroethidium labeling. Western blotting and real-time PCR were used to examine protein and mRNA expression levels, respectively.
Results: Retinal LCN2 expression was significantly upregulated after light exposure. Light exposure reduced the amplitudes of a- and b-waves on the ERG and the thickness of the outer nuclear layer and promoted photoreceptor apoptosis. These phenomena were clearly attenuated by LCN2 knockdown, whereas LCN2 overexpression had the opposite effects. The overexpression of LCN2 facilitated photoreceptor apoptosis by increasing ROS generation and Bim expression. On the opposite, LCN2 knockdown mitigated the generation of light-exposure-induced ROS and the activation of the Bim-mediated mitochondrial apoptotic pathway.
Conclusions: Light-induced LCN2 is a proapoptotic factor in the retina, and LCN2 knockdown protects photoreceptors from apoptosis by inhibiting ROS production and Bim expression. LCN2 is a potential therapeutic target for light-induced retinal degeneration.




  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
LCN2Humanretinal degeneration amelioratesISOLcn2 (Rattus norvegicus) RGD 
LCN2Humanretinal degeneration exacerbatesISOLcn2 (Rattus norvegicus) RGD 
Lcn2Ratretinal degeneration amelioratesIMP  RGD 
Lcn2Ratretinal degeneration exacerbatesIDA  RGD 
Lcn2Mouseretinal degeneration amelioratesISOLcn2 (Rattus norvegicus) RGD 
Lcn2Mouseretinal degeneration exacerbatesISOLcn2 (Rattus norvegicus) RGD 


Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
Lcn2Ratpositive regulation of neuron apoptotic process  IMP  RGD 
Lcn2Ratpositive regulation of reactive oxygen species metabolic process  IMP  RGD 
Lcn2Ratresponse to blue light  IEP  RGD 


Genes (Rattus norvegicus)
Lcn2  (lipocalin 2)

Genes (Mus musculus)
Lcn2  (lipocalin 2)

Genes (Homo sapiens)
LCN2  (lipocalin 2)