PMID- 25269915
OWN - NLM
STAT- MEDLINE
DCOM- 20150409
LR  - 20141001
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 127
IP  - 19
DP  - 2014
TI  - Glycogen synthase kinase-3: a key kinase in retinal neuron apoptosis in early 
      diabetic retinopathy.
PG  - 3464-70
AB  - BACKGROUND: Diabetes-related pathogenic factors can cause retinal ganglion cell 
      (RGC) apoptosis, but the specific mechanism is not very clear. The aim of this 
      study is to investigate the correlation between glycogen synthase kinase-3 
      (GSK-3) activation and retinal neuron apoptosis. METHODS: In an in vitro 
      experiment, the number of apoptotic RGC-5 cells differentiated by staurosporine 
      was evaluated via flow cytometry and nuclei staining using Hoechst 33258. GSK-3 
      phosphorylation and caspase-3 activation in RGC-5 cells after serum deprivation 
      were determined using Western blotting. Mitochondrial membrane potential was 
      detected using the dye 5, 5', 6, 6'tetrachloro-1, 1', 3, 3'-tetrethyl 
      benzimidalyl carbocyanine iodide, and reactive oxygen species (ROS) levels were 
      measured with dihydroethidium. In an in vivo experiment, the number of apoptotic 
      retinal neurons was evaluated via terminal transferase dUTP nick-end labeling 
      (TUNEL), and GSK-3 phosphorylation was determined using Western blotting, in the 
      retinal nerve epithelial tissue of rats in which diabetes was induced by 
      intravenous tail-vein injection of streptozotocin for 4 weeks. RESULTS: The 
      levels of phosphorylated Ser21/9 in GSK-3alpha/beta and p-T308/S473-AKT were lower and 
      the cleaved caspase-3 levels were higher in the serum-deprived model (P < 0.05). 
      Lithium chloride treatment was associated with a slower rate of apoptosis, 
      increased mitochondrial membrane potential, and decreased ROS levels in 
      differentiated RGC-5 cells (P < 0.05). The level of blood glucose and the number 
      of TUNEL-positive cells in the whole-mounted retinas were higher (P < 0.01), and 
      the levels of phosphorylated Ser21/9 in GSK-3alpha/beta and body weight were lower (P < 
      0.05). However, the thickness of the retinal nerve epithelial layer was not 
      significantly less in diabetic rats compared with control group. Lithium chloride 
      intravitreal injection increased the levels of phosphorylated Ser21/9 in GSK-3alpha/beta 
      and decreased TUNEL-positive cells in the whole-mounted retinas. CONCLUSION: 
      GSK-3 kinase is closely related to retinal neuron apoptosis, and the application 
      of the GSK-3 inhibitor lithium chloride can reduce retinal neuron apoptosis in 
      early diabetic retinopathy.
FAU - Li, Zhaohui
AU  - Li Z
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Ma, Ling
AU  - Ma L
AD  - Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China.
FAU - Chen, Xiaodong
AU  - Chen X
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Li, Yonghao
AU  - Li Y
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Li, Shiyi
AU  - Li S
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Zhang, Jinglin
AU  - Zhang J
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China.
FAU - Lu, Lin
AU  - Lu L
AD  - State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen 
      University, Guangzhou, Guangdong 510060, China. Email: lulin888@sohu.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - EC 2.7.11.26 (glycogen synthase kinase 3 alpha)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics/physiology
MH  - Cell Line
MH  - Cell Survival/physiology
MH  - Diabetic Retinopathy/*enzymology/genetics/*metabolism
MH  - Flow Cytometry
MH  - Glycogen Synthase Kinase 3/genetics/*metabolism
MH  - Male
MH  - Neurons/*cytology/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Retina/*cytology/*enzymology
EDAT- 2014/10/02 06:00
MHDA- 2015/04/10 06:00
CRDT- 2014/10/02 06:00
PHST- 2014/10/02 06:00 [entrez]
PHST- 2014/10/02 06:00 [pubmed]
PHST- 2015/04/10 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2014;127(19):3464-70.