Journal article
ERK- and Akt-Dependent Neuroprotection by Erythropoietin (EPO) against Glyoxal-AGEs via Modulation of Bcl-xL, Bax, and BAD
Investigative ophthalmology & visual science, v 51(1)
01 Jan 2010
PMID: 19628748
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
PURPOSE. To characterize the neuroprotective mechanisms of erythropoietin (EPO) against the stress of glyoxal-advanced glycation end products (AGEs) in retinal neuronal cells.
METHODS. Rat retinal organ culture, primary retinal neuron culture, and retinal cell line (R28 cell) culture under glyoxal-AGEs insult were used as in vitro models. Exogenous EPO was applied to these models. Retinal neuronal cell death was assessed by TUNEL, ethidium bromide/acridine orange staining, and cell viability assay. R28 cell proliferation was evaluated by BrdU incorporation and propidium iodide staining. Real-time RT-PCR and Western blot analysis were used to detect Bcl-xL, Bcl-2, Bax, BAD, and products of extracellular signal regulated kinase (ERK) and Akt pathways. Specific inhibitors and plasmids were used to pinpoint the roles of ERK and Akt pathways.
RESULTS. EPO protected the retinal cells from glyoxal-AGE-induced injury in a time-and dose-dependent fashion. The protective function of EPO was proved to be antiapoptotic, not pro-cell proliferative. Glyoxal upregulated Bax expression but suppressed Bcl-xL expression and BAD phosphorylation. In contrast, EPO enhanced BAD phosphorylation and Bcl-xL expression but downregulated Bax. The regulation of these apoptosis-related proteins by EPO was through ERK and Akt pathways.
CONCLUSIONS. These data demonstrate that exogenous EPO significantly attenuates the retinal neuronal cell death induced by glyoxal-AGEs by promoting antiapoptotic and suppressing apoptotic proteins. EPO/EPO receptor signaling through ERK and Akt pathways is pivotal in EPO neuroprotective mechanisms. (Invest Ophthalmol Vis Sci. 2010; 51: 35-46) DOI: 10.1167/iovs.09-3544
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Details
- Title
- ERK- and Akt-Dependent Neuroprotection by Erythropoietin (EPO) against Glyoxal-AGEs via Modulation of Bcl-xL, Bax, and BAD
- Creators
- Jianfeng Shen - Laboratory of Clinical Visual Sciences, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaYalan Wu - From the Laboratory of Clinical Visual Sciences, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China;Jing-Ying Xu - From the Laboratory of Clinical Visual Sciences, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China;Jingfa Zhang - From the Laboratory of Clinical Visual Sciences, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China;Stephen H. Sinclair - Drexel UniversityMyron Yanoff - Drexel UniversityGuoxu Xu - Suzhou Univ, Affiliated Hosp 2, Dept Ophthalmol, Suzhou 215006, Peoples R ChinaWeiye Li - From the Laboratory of Clinical Visual Sciences, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai, China;Guo-Tong Xu - Department of Ophthalmology, Second Affiliated Hospital of Suzhou University, Suzhou, China; and
- Publication Details
- Investigative ophthalmology & visual science, v 51(1)
- Publisher
- Assoc Research Vision Ophthalmology Inc
- Number of pages
- 12
- Grant note
- 054107058; 08410701200; 08ZR1422100 / Shanghai Science and Technology Committee; Shanghai Science & Technology Committee Clear Vision Foundation, Philadelphia, Pennsylvania 2004CB720304; 2007CB948004 / Ministry of Science and Technology; Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Ophthalmology [Historical]
- Web of Science ID
- WOS:000273264200007
- Scopus ID
- 2-s2.0-75749093639
- Other Identifier
- 991019167765604721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Ophthalmology