Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin β
Meprin metalloproteases play a role in the pathology of ischemia/reperfusion- (IR-) induced renal injury. The endoplasmic reticulum-associated protein, osteosarcoma-9 (OS-9), has been shown to interact with the carboxyl-terminal tail of meprin β. More importantly, OS-9 interacts with the hypoxia ind...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | International Journal of Nephrology |
| Online Access: | http://dx.doi.org/10.1155/2016/2851803 |
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| author | Barry Lee Martin Sabena Michelle Conley Regine Simone Harris Corshe Devon Stanley Jean-Marie Vianney Niyitegeka Elimelda Moige Ongeri |
| author_facet | Barry Lee Martin Sabena Michelle Conley Regine Simone Harris Corshe Devon Stanley Jean-Marie Vianney Niyitegeka Elimelda Moige Ongeri |
| author_sort | Barry Lee Martin |
| collection | DOAJ |
| description | Meprin metalloproteases play a role in the pathology of ischemia/reperfusion- (IR-) induced renal injury. The endoplasmic reticulum-associated protein, osteosarcoma-9 (OS-9), has been shown to interact with the carboxyl-terminal tail of meprin β. More importantly, OS-9 interacts with the hypoxia inducible factor-1α (HIF-1α) and the prolyl-hydroxylase, proteins which mediate the cell’s response to hypoxia. To determine if OS-9 is a meprin substrate, kidney proteins from meprin αβ knockout mice (αβKO) (which lack endogenous meprins) and purified human OS-9 were incubated with activated forms of meprin A and meprin B, and Western blot analysis was used to evaluate proteolytic processing of OS-9. Fragmentation of OS-9 was observed in reactions with meprin B, but not meprin A. To determine whether meprin B cleaves OS-9 in vivo, wild-type (WT) and meprin αβKO mice were subjected to IR-induced renal injury. Fragmentation of OS-9 was observed in kidney proteins from WT mice subjected to IR, but not in meprin αβKO counterparts. Transfection of kidney cells (MDCK and HEK293) with meprin β cDNA prevented accumulation of OS-9 following exposure to the hypoxia mimic, CoCl2. These data suggest that meprin β interaction with OS-9 plays a role in the hypoxia response associated with IR-induced renal injury. |
| format | Article |
| id | doaj-art-af9f35f27b7240918d053d1bb9d68eb0 |
| institution | Kabale University |
| issn | 2090-214X 2090-2158 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | International Journal of Nephrology |
| spelling | doaj-art-af9f35f27b7240918d053d1bb9d68eb02025-02-03T05:50:52ZengWileyInternational Journal of Nephrology2090-214X2090-21582016-01-01201610.1155/2016/28518032851803Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin βBarry Lee Martin0Sabena Michelle Conley1Regine Simone Harris2Corshe Devon Stanley3Jean-Marie Vianney Niyitegeka4Elimelda Moige Ongeri5Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USADepartment of Biology, North Carolina A&T State University, Greensboro, NC 27411, USADepartment of Biology, North Carolina A&T State University, Greensboro, NC 27411, USADepartment of Biology, North Carolina A&T State University, Greensboro, NC 27411, USADepartment of Biology, North Carolina A&T State University, Greensboro, NC 27411, USADepartment of Biology, North Carolina A&T State University, Greensboro, NC 27411, USAMeprin metalloproteases play a role in the pathology of ischemia/reperfusion- (IR-) induced renal injury. The endoplasmic reticulum-associated protein, osteosarcoma-9 (OS-9), has been shown to interact with the carboxyl-terminal tail of meprin β. More importantly, OS-9 interacts with the hypoxia inducible factor-1α (HIF-1α) and the prolyl-hydroxylase, proteins which mediate the cell’s response to hypoxia. To determine if OS-9 is a meprin substrate, kidney proteins from meprin αβ knockout mice (αβKO) (which lack endogenous meprins) and purified human OS-9 were incubated with activated forms of meprin A and meprin B, and Western blot analysis was used to evaluate proteolytic processing of OS-9. Fragmentation of OS-9 was observed in reactions with meprin B, but not meprin A. To determine whether meprin B cleaves OS-9 in vivo, wild-type (WT) and meprin αβKO mice were subjected to IR-induced renal injury. Fragmentation of OS-9 was observed in kidney proteins from WT mice subjected to IR, but not in meprin αβKO counterparts. Transfection of kidney cells (MDCK and HEK293) with meprin β cDNA prevented accumulation of OS-9 following exposure to the hypoxia mimic, CoCl2. These data suggest that meprin β interaction with OS-9 plays a role in the hypoxia response associated with IR-induced renal injury.http://dx.doi.org/10.1155/2016/2851803 |
| spellingShingle | Barry Lee Martin Sabena Michelle Conley Regine Simone Harris Corshe Devon Stanley Jean-Marie Vianney Niyitegeka Elimelda Moige Ongeri Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin β International Journal of Nephrology |
| title | Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin β |
| title_full | Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin β |
| title_fullStr | Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin β |
| title_full_unstemmed | Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin β |
| title_short | Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin β |
| title_sort | hypoxia associated proteolytic processing of os 9 by the metalloproteinase meprin β |
| url | http://dx.doi.org/10.1155/2016/2851803 |
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