Expression modification of uncoupling proteins and MnSOD in retinal endothelial cells and pericytes induced by high glucose: The role of reactive oxygen species in diabetic retinopathy
Abstract
Uncoupling proteins (UCPs) are mitochondrial transporters present in the inner membrane of mitochondria. They belong to the family of anion mitochondrial carriers. UCPs could act as proton carriers activated by metabolites and create a shunt between complexes of the respiratory chain and ATP synthase. The increased leakiness of the mitochondrial inner membrane to protons may be to minimize superoxide production by limiting the maximum Deltamu(H+). The purpose of this study was to detect UCP expression in retinal capillary cells and their modification in high levels of glucose. The role of reactive oxygen species (ROS) of mitochondria and UCPs in pathogenesis of diabetic retinopathy was investigated. Bovine retinal capillary endothelial cells and pericytes were cultured with selective culture media, respectively. Passage cells were cultured in three different glucose concentrations (5, 23, 30 mM) until passage four. ROS changes in mitochondria of these cells in different glucose concentrations were detected with scanning laser confocal microscopy (SLCM). The mitochondria membrane potential (Deltapsi), cell death rate and apoptosis rate were measured with flowing cytometry. UCP expression in retinal capillary cells was detected by immunocytochemistry. Expression and modification of MnSOD and uncoupling proteins (UCPs) in different concentrations of glucose were detected by means of semi-quantitative RT-PCR. ROS in mitochondria of both endothelial cells and pericytes increased as the glucose concentration of media increased. Deltapsi and cell death rate of endothelial cells increased also. ROS was correlated to Deltapsi and cell death rate positively in endothelial cells. No difference in Deltapsi and cell death rate among different glucose levels was found in pericytes. Apoptosis rate of endothelial cells and pericytes in high glucose levels was higher than that in lower glucose levels. UCP1 and UCP2 were expressed in cultured retinal capillary cells whereas UCP3 was not. At high levels of glucose, expression of UCP1, UCP2 and MnSOD increased to accommodate ROS production compensatively. The compensative mechanism disappeared when glucose concentration was too high (30 mM). The results of this study showed that increasing mitochondrial ROS could be induced by high glucose concentration. Those proteins related to antioxidation mechanism, such as MnSOD and UCPs, could exert compensative action to a certain extent. This compensative action was insufficient when the glucose concentration was too high.
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In cultured retinal capillary cells exposed to high glucose, UCP2 expression is increased.
“Cui et al. (76) reported that UCP2 expression was increased in cultured retinal capillary cells exposed to high glucose.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [76]
The induced uncoupling proteins in retinal capillary cells included UCP1, generally expressed only in brown fat.
“Oddly, the induced UCPs included UCP1, generally expressed only in brown fat.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [76]
High glucose increased uncoupling protein expression and MnSOD in bovine retinal capillary endothelial cells and pericytes.
“These authors also noted increased uncoupling protein expression and MnSOD, suggesting mitochondrial compensation for ROS.”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [76]
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Self-citation
- Authors
- Cui, Y., Xu, X., Bi, H., Zhu, Q., Wu, J., Xia, X., Ren, Q., & Ho, P. C. P.
- Affiliations
- Shanghai First People's Hospital (CN)
- Shandong Shierming Eye Hospital (CN)
- Corresponding author
- Xu, Xun
- Venue
- Experimental Eye Research
- Publisher
- Elsevier BV
- Published
- 2006-10
- Volume
- 83
- Issue
- 4
- Pages
- 807-816
- ISSN
- 0014-4835 (ISSN-L)
- OpenAlex
- W1981664971
- Cited by
- 159
- References
- 26
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 15 · 2018: 6 · 2017: 10 · 2016: 5 · 2015: 11 · 2014: 13 · 2013: 9 · 2012: 13
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Eye Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Key Research and Development Program of China
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- uncoupling proteins, UCP1, UCP2, UCP3, manganese superoxide dismutase, reactive oxygen species, mitochondrial reactive oxygen species, diabetic retinopathy, high glucose, retinal endothelial cells, retinal pericytes, mitochondrial membrane potential, apoptosis, oxidative stress, antioxidant defense, mitochondrial uncoupling, proton leak, superoxide production
- MeSH terms
- Uncoupling Protein 2, Uncoupling Protein 1, Animals, Cattle, Cells, Cultured, Diabetic Retinopathy, Dose-Response Relationship, Drug, Gene Expression Regulation, Glucose, Ion Channels, Membrane Potentials, Mitochondria, Retina, Superoxide Dismutase, Cell Death, Apoptosis, Reactive Oxygen Species, Microscopy, Confocal, Reverse Transcriptase Polymerase Chain Reaction, Pericytes, Mitochondrial Proteins, Endothelial Cells
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