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Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy
OBJECTIVE: Paraoxonase (PON) exhibits esterase activity (PON-AREase) and lactonase activity (PON-HCTLase), which prevent LDL oxidation and detoxify homocysteine thiolactone (HCTL). The role of HCTL and PON-HCTLase as a risk factor for the microvascular complication in diabetic retinopathy at the lev...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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American Diabetes Association
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928358/ https://www.ncbi.nlm.nih.gov/pubmed/20551012 http://dx.doi.org/10.2337/dc10-0132 |
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author | Barathi, Subramaniam Angayarkanni, Narayanasamy Pasupathi, Aarthi Natarajan, Sulochana Konerirajapuram Pukraj, Rishi Dhupper, Maneesh Velpandian, Thirumurthy Muralidharan, Charanya Sivashanmugham, Muthukumaran |
author_facet | Barathi, Subramaniam Angayarkanni, Narayanasamy Pasupathi, Aarthi Natarajan, Sulochana Konerirajapuram Pukraj, Rishi Dhupper, Maneesh Velpandian, Thirumurthy Muralidharan, Charanya Sivashanmugham, Muthukumaran |
author_sort | Barathi, Subramaniam |
collection | PubMed |
description | OBJECTIVE: Paraoxonase (PON) exhibits esterase activity (PON-AREase) and lactonase activity (PON-HCTLase), which prevent LDL oxidation and detoxify homocysteine thiolactone (HCTL). The role of HCTL and PON-HCTLase as a risk factor for the microvascular complication in diabetic retinopathy at the level of vitreous has not been investigated. RESEARCH DESIGN AND METHODS: Undiluted vitreous from patients with proliferative diabetic retinopathy (PDR) (n = 13) and macular hole (MH) (n = 8) was used to determine PON-HCTLase and PON-AREase activity spectrophotometrically. HCTL levels were detected by liquid chromatography–tandem mass spectrometry. In vitro studies were done in primary cultures of bovine retinal capillary endothelial cells (BRECs) to determine the dose- and time-dependent effect of HCTL and homocysteine (Hcys) on PON-HCTLase activity, as well as to determine mRNA expression of PON by RT-PCR. RESULTS: A significant increase in HCTL and PON-HCTLase activity was observed in PDR compared with MH (P = 0.036, P = 0.001), with a significant positive correlation between them (r = 0.77, P = 0.03). The in vitro studies on BRECs showed a dose- and time-dependent increase in the PON-HCTLase activity and mRNA expression of PON2 when exposed to HCTL and Hcys. CONCLUSIONS: This is the first study showing elevated levels of vitreous HCTL and PON-HCTLase activity in PDR. These elevations are probably a protective effect to eliminate HCTL, which mediates endothelial cell dysfunction. Thus, vitreous levels of HCTL and PON activity can be markers of diabetic retinopathy. The bioinformatics analysis reveals that the structure and function of PON that can be modulated by hyperhomocysteinemia in PDR can affect the dual-enzyme activity of PON. |
format | Text |
id | pubmed-2928358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Diabetes Association |
record_format | MEDLINE/PubMed |
spelling | pubmed-29283582011-09-01 Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy Barathi, Subramaniam Angayarkanni, Narayanasamy Pasupathi, Aarthi Natarajan, Sulochana Konerirajapuram Pukraj, Rishi Dhupper, Maneesh Velpandian, Thirumurthy Muralidharan, Charanya Sivashanmugham, Muthukumaran Diabetes Care Original Research OBJECTIVE: Paraoxonase (PON) exhibits esterase activity (PON-AREase) and lactonase activity (PON-HCTLase), which prevent LDL oxidation and detoxify homocysteine thiolactone (HCTL). The role of HCTL and PON-HCTLase as a risk factor for the microvascular complication in diabetic retinopathy at the level of vitreous has not been investigated. RESEARCH DESIGN AND METHODS: Undiluted vitreous from patients with proliferative diabetic retinopathy (PDR) (n = 13) and macular hole (MH) (n = 8) was used to determine PON-HCTLase and PON-AREase activity spectrophotometrically. HCTL levels were detected by liquid chromatography–tandem mass spectrometry. In vitro studies were done in primary cultures of bovine retinal capillary endothelial cells (BRECs) to determine the dose- and time-dependent effect of HCTL and homocysteine (Hcys) on PON-HCTLase activity, as well as to determine mRNA expression of PON by RT-PCR. RESULTS: A significant increase in HCTL and PON-HCTLase activity was observed in PDR compared with MH (P = 0.036, P = 0.001), with a significant positive correlation between them (r = 0.77, P = 0.03). The in vitro studies on BRECs showed a dose- and time-dependent increase in the PON-HCTLase activity and mRNA expression of PON2 when exposed to HCTL and Hcys. CONCLUSIONS: This is the first study showing elevated levels of vitreous HCTL and PON-HCTLase activity in PDR. These elevations are probably a protective effect to eliminate HCTL, which mediates endothelial cell dysfunction. Thus, vitreous levels of HCTL and PON activity can be markers of diabetic retinopathy. The bioinformatics analysis reveals that the structure and function of PON that can be modulated by hyperhomocysteinemia in PDR can affect the dual-enzyme activity of PON. American Diabetes Association 2010-09 2010-06-14 /pmc/articles/PMC2928358/ /pubmed/20551012 http://dx.doi.org/10.2337/dc10-0132 Text en © 2010 by the American Diabetes Association. https://creativecommons.org/licenses/by-nc-nd/3.0/Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ (https://creativecommons.org/licenses/by-nc-nd/3.0/) for details. |
spellingShingle | Original Research Barathi, Subramaniam Angayarkanni, Narayanasamy Pasupathi, Aarthi Natarajan, Sulochana Konerirajapuram Pukraj, Rishi Dhupper, Maneesh Velpandian, Thirumurthy Muralidharan, Charanya Sivashanmugham, Muthukumaran Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy |
title | Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy |
title_full | Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy |
title_fullStr | Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy |
title_full_unstemmed | Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy |
title_short | Homocysteinethiolactone and Paraoxonase: Novel markers of diabetic retinopathy |
title_sort | homocysteinethiolactone and paraoxonase: novel markers of diabetic retinopathy |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928358/ https://www.ncbi.nlm.nih.gov/pubmed/20551012 http://dx.doi.org/10.2337/dc10-0132 |
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