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Does oxidative stress play any role in diabetic cataract formation? ----Re-evaluation using a thioltransferase gene knockout mouse model.
Exp Eye Res. 2017 08; 161:36-42.EE

Abstract

Oxidative stress is a known risk factor in senile cataract formation. In recent years, it has been suggested that oxidation may also be associated with cataract induced by hyperglycemia, but this concept has not been well examined or validated. Since thioltransferase (TTase) is one of the key enzymes that regulates redox homeostasis and protects against oxidative stress in the lens, we have used TTase gene knockout (KO) mice as a model to examine this new concept. Lenses from 4 months old TTase KO and wild-type (WT) mice were incubated in TC199 culture medium containing 30 mM glucose for 48 h. Each lens was assessed for opacity, graded by LOCSII system, and the wet weight was recorded after which it was homogenized in lysis buffer and analyzed for water-soluble protein and free glutathione (GSH). In vivo studies were carried out using 4 months old TTase KO and WT mouse groups. Each mouse received two consecutive days of intraperitoneal streptozotozin (STZ) injections to induce diabetes. The lenses were examined weekly for 4 weeks using a slit-lamp biomicroscope, and then extracted and analyzed for levels of GSH, water-soluble protein, ATP and protein-GSH mixed disulfide (PSSG). TTase KO lenses cultured in high glucose developed a mild cortical opacity but slightly more than that of the WT lenses. Both groups had similar contents of soluble proteins and GSH. Exposure to high glucose did not change the soluble protein level but did suppress GSH by 20% in lenses with or without TTase. STZ-induced diabetic KO mice also developed a higher degree of mild cortical lens opacity compared to that of the diabetic WT controls. Similar 15-20% losses in lens GSH and ATP were found after one-month induced diabetes in WT and KO mice. There was a 20% greater amount of PSSG in the lenses of TTase KO than the WT control. Under diabetic condition, both groups displayed more glutathionylated proteins in the beta-actin (42 kDa) and lens crystallin proteins (18-22 kDa) regions, and some additional modified proteins at 15-17 kDa and 60-70 kDa, with a total 20-30% PSSG increment in both groups. In conclusion, we have found that hyperglycemia induced some oxidative stress-associated biochemical changes with mild lens opacity in both WT and KO mice. However, these changes were only marginally higher in the TTase KO mouse than that of the WT control, suggesting that TTase deletion may only play a minor role in the early stage of hyperglycemia-induced cataract formation in the mice.

Authors+Show Affiliations

Department of Ophthalmology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China; School of Veterinary Medicine and Biomedical Sciences, Lincoln, NE, USA.Department of Ophthalmology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.School of Veterinary Medicine and Biomedical Sciences, Lincoln, NE, USA; Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE, USA; Department of Ophthalmology, University of Nebraska-Medical Center, Omaha, NE, USA. Electronic address: mlou1@unl.edu.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

28579033

Citation

Zhang, Jie, et al. "Does Oxidative Stress Play Any Role in Diabetic Cataract Formation? ----Re-evaluation Using a Thioltransferase Gene Knockout Mouse Model." Experimental Eye Research, vol. 161, 2017, pp. 36-42.
Zhang J, Yan H, Lou MF. Does oxidative stress play any role in diabetic cataract formation? ----Re-evaluation using a thioltransferase gene knockout mouse model. Exp Eye Res. 2017;161:36-42.
Zhang, J., Yan, H., & Lou, M. F. (2017). Does oxidative stress play any role in diabetic cataract formation? ----Re-evaluation using a thioltransferase gene knockout mouse model. Experimental Eye Research, 161, 36-42. https://doi.org/10.1016/j.exer.2017.05.014
Zhang J, Yan H, Lou MF. Does Oxidative Stress Play Any Role in Diabetic Cataract Formation? ----Re-evaluation Using a Thioltransferase Gene Knockout Mouse Model. Exp Eye Res. 2017;161:36-42. PubMed PMID: 28579033.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Does oxidative stress play any role in diabetic cataract formation? ----Re-evaluation using a thioltransferase gene knockout mouse model. AU - Zhang,Jie, AU - Yan,Hong, AU - Lou,Marjorie F, Y1 - 2017/06/01/ PY - 2017/03/01/received PY - 2017/05/11/revised PY - 2017/05/31/accepted PY - 2017/6/6/pubmed PY - 2017/8/22/medline PY - 2017/6/6/entrez KW - Cataract KW - Diabetes KW - Gene knockout mice KW - Glucose KW - Glutathionylated proteins KW - Osmotic stress KW - Oxidative stress KW - Thioltransferase SP - 36 EP - 42 JF - Experimental eye research JO - Exp Eye Res VL - 161 N2 - Oxidative stress is a known risk factor in senile cataract formation. In recent years, it has been suggested that oxidation may also be associated with cataract induced by hyperglycemia, but this concept has not been well examined or validated. Since thioltransferase (TTase) is one of the key enzymes that regulates redox homeostasis and protects against oxidative stress in the lens, we have used TTase gene knockout (KO) mice as a model to examine this new concept. Lenses from 4 months old TTase KO and wild-type (WT) mice were incubated in TC199 culture medium containing 30 mM glucose for 48 h. Each lens was assessed for opacity, graded by LOCSII system, and the wet weight was recorded after which it was homogenized in lysis buffer and analyzed for water-soluble protein and free glutathione (GSH). In vivo studies were carried out using 4 months old TTase KO and WT mouse groups. Each mouse received two consecutive days of intraperitoneal streptozotozin (STZ) injections to induce diabetes. The lenses were examined weekly for 4 weeks using a slit-lamp biomicroscope, and then extracted and analyzed for levels of GSH, water-soluble protein, ATP and protein-GSH mixed disulfide (PSSG). TTase KO lenses cultured in high glucose developed a mild cortical opacity but slightly more than that of the WT lenses. Both groups had similar contents of soluble proteins and GSH. Exposure to high glucose did not change the soluble protein level but did suppress GSH by 20% in lenses with or without TTase. STZ-induced diabetic KO mice also developed a higher degree of mild cortical lens opacity compared to that of the diabetic WT controls. Similar 15-20% losses in lens GSH and ATP were found after one-month induced diabetes in WT and KO mice. There was a 20% greater amount of PSSG in the lenses of TTase KO than the WT control. Under diabetic condition, both groups displayed more glutathionylated proteins in the beta-actin (42 kDa) and lens crystallin proteins (18-22 kDa) regions, and some additional modified proteins at 15-17 kDa and 60-70 kDa, with a total 20-30% PSSG increment in both groups. In conclusion, we have found that hyperglycemia induced some oxidative stress-associated biochemical changes with mild lens opacity in both WT and KO mice. However, these changes were only marginally higher in the TTase KO mouse than that of the WT control, suggesting that TTase deletion may only play a minor role in the early stage of hyperglycemia-induced cataract formation in the mice. SN - 1096-0007 UR - https://www.unboundmedicine.com/medline/citation/28579033/Does_oxidative_stress_play_any_role_in_diabetic_cataract_formation_____Re_evaluation_using_a_thioltransferase_gene_knockout_mouse_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4835(17)30160-4 DB - PRIME DP - Unbound Medicine ER -