Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions
Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 ex...
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| Veröffentlicht in: | Kidney international 2009-10, Vol.76 (8), p.838-848 |
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| creator | Lee, Sang Choel Han, Seung Hyeok Li, Jin Ji Lee, Sun Ha Jung, Dong-Sub Kwak, Seung-Jae Kim, Seung Hye Kim, Dong Ki Yoo, Tae-Hyun Kim, Jin Hyun Chang, Se-Ho Han, Dae Suk Kang, Shin-Wook |
| description | Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions. |
| doi_str_mv | 10.1038/ki.2009.286 |
| format | Article |
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Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.</description><identifier>ISSN: 0085-2538</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1038/ki.2009.286</identifier><identifier>PMID: 19657327</identifier><identifier>CODEN: KDYIA5</identifier><language>eng</language><publisher>Basingstoke: Elsevier Inc</publisher><subject>Animals ; apoptosis ; Apoptosis - drug effects ; bcl-2-Associated X Protein - metabolism ; Biological and medical sciences ; Caspase 3 - metabolism ; Cells, Cultured ; Diabetes Mellitus, Experimental - complications ; Diabetes Mellitus, Experimental - enzymology ; Diabetes Mellitus, Experimental - pathology ; Diabetes. Impaired glucose tolerance ; Diabetic Nephropathies - enzymology ; Diabetic Nephropathies - etiology ; Diabetic Nephropathies - pathology ; Diabetic Nephropathies - prevention & control ; diabetic nephropathy ; Endocrine pancreas. Apud cells (diseases) ; Endocrinopathies ; Enzyme Inhibitors - pharmacology ; Etiopathogenesis. Screening. Investigations. Target tissue resistance ; Female ; Glucose - metabolism ; Heme Oxygenase (Decyclizing) - metabolism ; heme oxygenase-1 ; Heme Oxygenase-1 - antagonists & inhibitors ; Heme Oxygenase-1 - genetics ; Heme Oxygenase-1 - metabolism ; Hemin - pharmacology ; high glucose ; Hypoxia-Inducible Factor 1 - metabolism ; Kidneys ; Male ; Medical sciences ; Membrane Proteins - metabolism ; Mice ; Nephrology. Urinary tract diseases ; podocyte ; Podocytes - drug effects ; Podocytes - enzymology ; Podocytes - pathology ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Protoporphyrins - pharmacology ; Rats ; Rats, Sprague-Dawley ; RNA Interference ; Up-Regulation ; Urinary system involvement in other diseases. Miscellaneous</subject><ispartof>Kidney international, 2009-10, Vol.76 (8), p.838-848</ispartof><rights>2009 International Society of Nephrology</rights><rights>2009 INIST-CNRS</rights><rights>Copyright Nature Publishing Group Oct 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-23b2a71352bf037e5b4f088924694cc583eefb6f987c964bbec592243d44e7463</citedby><cites>FETCH-LOGICAL-c518t-23b2a71352bf037e5b4f088924694cc583eefb6f987c964bbec592243d44e7463</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/210120255?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>315,781,785,27929,27930,64390,64392,64394,72474</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=22014220$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19657327$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lee, Sang Choel</creatorcontrib><creatorcontrib>Han, Seung Hyeok</creatorcontrib><creatorcontrib>Li, Jin Ji</creatorcontrib><creatorcontrib>Lee, Sun Ha</creatorcontrib><creatorcontrib>Jung, Dong-Sub</creatorcontrib><creatorcontrib>Kwak, Seung-Jae</creatorcontrib><creatorcontrib>Kim, Seung Hye</creatorcontrib><creatorcontrib>Kim, Dong Ki</creatorcontrib><creatorcontrib>Yoo, Tae-Hyun</creatorcontrib><creatorcontrib>Kim, Jin Hyun</creatorcontrib><creatorcontrib>Chang, Se-Ho</creatorcontrib><creatorcontrib>Han, Dae Suk</creatorcontrib><creatorcontrib>Kang, Shin-Wook</creatorcontrib><title>Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions</title><title>Kidney international</title><addtitle>Kidney Int</addtitle><description>Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.</description><subject>Animals</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>bcl-2-Associated X Protein - metabolism</subject><subject>Biological and medical sciences</subject><subject>Caspase 3 - metabolism</subject><subject>Cells, Cultured</subject><subject>Diabetes Mellitus, Experimental - complications</subject><subject>Diabetes Mellitus, Experimental - enzymology</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>Diabetes. Impaired glucose tolerance</subject><subject>Diabetic Nephropathies - enzymology</subject><subject>Diabetic Nephropathies - etiology</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Diabetic Nephropathies - prevention & control</subject><subject>diabetic nephropathy</subject><subject>Endocrine pancreas. Apud cells (diseases)</subject><subject>Endocrinopathies</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Etiopathogenesis. Screening. Investigations. Target tissue resistance</subject><subject>Female</subject><subject>Glucose - metabolism</subject><subject>Heme Oxygenase (Decyclizing) - metabolism</subject><subject>heme oxygenase-1</subject><subject>Heme Oxygenase-1 - antagonists & inhibitors</subject><subject>Heme Oxygenase-1 - genetics</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Hemin - pharmacology</subject><subject>high glucose</subject><subject>Hypoxia-Inducible Factor 1 - metabolism</subject><subject>Kidneys</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>Nephrology. Urinary tract diseases</subject><subject>podocyte</subject><subject>Podocytes - drug effects</subject><subject>Podocytes - enzymology</subject><subject>Podocytes - pathology</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Protoporphyrins - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>RNA Interference</subject><subject>Up-Regulation</subject><subject>Urinary system involvement in other diseases. 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Impaired glucose tolerance</topic><topic>Diabetic Nephropathies - enzymology</topic><topic>Diabetic Nephropathies - etiology</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Diabetic Nephropathies - prevention & control</topic><topic>diabetic nephropathy</topic><topic>Endocrine pancreas. Apud cells (diseases)</topic><topic>Endocrinopathies</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Etiopathogenesis. Screening. Investigations. Target tissue resistance</topic><topic>Female</topic><topic>Glucose - metabolism</topic><topic>Heme Oxygenase (Decyclizing) - metabolism</topic><topic>heme oxygenase-1</topic><topic>Heme Oxygenase-1 - antagonists & inhibitors</topic><topic>Heme Oxygenase-1 - genetics</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Hemin - pharmacology</topic><topic>high glucose</topic><topic>Hypoxia-Inducible Factor 1 - metabolism</topic><topic>Kidneys</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>Nephrology. Urinary tract diseases</topic><topic>podocyte</topic><topic>Podocytes - drug effects</topic><topic>Podocytes - enzymology</topic><topic>Podocytes - pathology</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Protoporphyrins - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>RNA Interference</topic><topic>Up-Regulation</topic><topic>Urinary system involvement in other diseases. 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Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.</abstract><cop>Basingstoke</cop><pub>Elsevier Inc</pub><pmid>19657327</pmid><doi>10.1038/ki.2009.286</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals apoptosis Apoptosis - drug effects bcl-2-Associated X Protein - metabolism Biological and medical sciences Caspase 3 - metabolism Cells, Cultured Diabetes Mellitus, Experimental - complications Diabetes Mellitus, Experimental - enzymology Diabetes Mellitus, Experimental - pathology Diabetes. Impaired glucose tolerance Diabetic Nephropathies - enzymology Diabetic Nephropathies - etiology Diabetic Nephropathies - pathology Diabetic Nephropathies - prevention & control diabetic nephropathy Endocrine pancreas. Apud cells (diseases) Endocrinopathies Enzyme Inhibitors - pharmacology Etiopathogenesis. Screening. Investigations. Target tissue resistance Female Glucose - metabolism Heme Oxygenase (Decyclizing) - metabolism heme oxygenase-1 Heme Oxygenase-1 - antagonists & inhibitors Heme Oxygenase-1 - genetics Heme Oxygenase-1 - metabolism Hemin - pharmacology high glucose Hypoxia-Inducible Factor 1 - metabolism Kidneys Male Medical sciences Membrane Proteins - metabolism Mice Nephrology. Urinary tract diseases podocyte Podocytes - drug effects Podocytes - enzymology Podocytes - pathology Proto-Oncogene Proteins c-bcl-2 - metabolism Protoporphyrins - pharmacology Rats Rats, Sprague-Dawley RNA Interference Up-Regulation Urinary system involvement in other diseases. Miscellaneous |
| title | Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions |
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