Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice
Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to eval...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | International Journal of Hypertension |
| Online Access: | http://dx.doi.org/10.1155/2012/740203 |
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| author | Tomoko Kawakami Nitin Puri Komal Sodhi Lars Bellner Toru Takahashi Kiyoshi Morita Rita Rezzani Tim D. Oury Nader G. Abraham |
| author_facet | Tomoko Kawakami Nitin Puri Komal Sodhi Lars Bellner Toru Takahashi Kiyoshi Morita Rita Rezzani Tim D. Oury Nader G. Abraham |
| author_sort | Tomoko Kawakami |
| collection | DOAJ |
| description | Heme oxygenase (HO) system is one of the key regulators of cellular redox
homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However,
recent reports have suggested an inhibitory effect of ROS on HO activity. In light of
these conflicting reports, this study was designed to evaluate effects of chronic oxidative
stress on HO system and its role in contributing towards patho-physiological
abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO
animals. Experiments were performed in WT and EC-SOD(−/−) mice treated with and
without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, elevated blood pressure, impaired endothelial function, reduced p-eNOS, p-AKT and increased HO-1 expression;
although, HO activity was significantly (P<0.05) attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P<0.05). CoPP, in EC-SOD(−/−) mice, enhanced HO activity (P<0.05) and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/−) mice. |
| format | Article |
| id | doaj-art-0f2592d080ee43a0b0e726e9e6997715 |
| institution | Kabale University |
| issn | 2090-0384 2090-0392 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Hypertension |
| spelling | doaj-art-0f2592d080ee43a0b0e726e9e69977152025-02-03T01:20:44ZengWileyInternational Journal of Hypertension2090-03842090-03922012-01-01201210.1155/2012/740203740203Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout MiceTomoko Kawakami0Nitin Puri1Komal Sodhi2Lars Bellner3Toru Takahashi4Kiyoshi Morita5Rita Rezzani6Tim D. Oury7Nader G. Abraham8Department of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama, JapanDepartment of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH, 43614, USADepartment of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH, 43614, USADepartment of Pharmacology, New York Medical College, Valhalla, NY 10595, USADepartment of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama, JapanDepartment of Anesthesiology and Resuscitology, Okayama University Medical School, Okayama, JapanDivision of Human Anatomy, Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, ItalyDepartment of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Physiology & Pharmacology, University of Toledo College of Medicine, Toledo, OH, 43614, USAHeme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD(−/−) mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, elevated blood pressure, impaired endothelial function, reduced p-eNOS, p-AKT and increased HO-1 expression; although, HO activity was significantly (P<0.05) attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P<0.05). CoPP, in EC-SOD(−/−) mice, enhanced HO activity (P<0.05) and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/−) mice.http://dx.doi.org/10.1155/2012/740203 |
| spellingShingle | Tomoko Kawakami Nitin Puri Komal Sodhi Lars Bellner Toru Takahashi Kiyoshi Morita Rita Rezzani Tim D. Oury Nader G. Abraham Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice International Journal of Hypertension |
| title | Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice |
| title_full | Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice |
| title_fullStr | Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice |
| title_full_unstemmed | Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice |
| title_short | Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice |
| title_sort | reciprocal effects of oxidative stress on heme oxygenase expression and activity contributes to reno vascular abnormalities in ec sod knockout mice |
| url | http://dx.doi.org/10.1155/2012/740203 |
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