title: High glucose induces mitochondrial dysfunction and apoptosis in human retinal pigment epithelium cells via promoting SOCS1 and Fas/FasL signaling.
abstract: Diabetic retinopathy (DR) is one of the most serious complications of diabetes mellitus (DM), however, the contribution of high glucose (HG) or hyperglycemia to DR is far from fully understanding. In the present study, we examined the expression of Fas/FasL signaling and suppressors of cytokine signaling (SOCS)1 and 3 in HG-induced human retinal pigment epithelium cells (ARPE-19 cells). And then we investigated the regulatory role of both Fas and SOCS1 in HG-induced mitochondrial dysfunction and apoptosis. Results demonstrated that HG with more than 40mM induced mitochondrial dysfunction via reducing mitochondrial membrane potential (MMP) and via inhibiting the Bcl-2 level, which is the upstream signaling of mitochondria in ARPE-19 cells. HG also upreuglated the Fas signaling and SOCS levels probably via promoting JAK/STAT signaling in ARPE-19 cells. Moreover, the exogenous Fas or entogenous overexpressed SOCS1 accentuated the HG-induced mitochondrial dysfunction and apoptosis, whereas the knockdown of either Fas or SOCS1 reduced the HG-induced mitochondria dysfunction and apoptosis. Thus, the present study confirmed that both Fas/FasL signaling and SOCS1 promoted the HG-induced mitochondrial dysfunction and apoptosis. These results implies the key regulatory role of Fas signaling and SOCS in DR.
authors.affiliation: Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310009, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310009, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ma
authors.affiliation: Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310009, China.
authors.forename: Panpan
authors.initials: P
authors.lastname: Ye
authors.affiliation: Eye Center, The 2nd Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China; Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou 310009, China. Electronic address: kaijwang@126.com.
authors.forename: Kaijun
authors.initials: K
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D003930:Diabetic Retinopathy / Q000503:physiopathology; D053222:Fas Ligand Protein / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism*
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D005947:Glucose
keywords: Apoptosis; Fas; High glucose; Mitochondrial dysfunction; Retinal pigment epithelium cells; Suppressor of cytokine signaling 1