title: Hypoxia Associated Proteolytic Processing of OS-9 by the Metalloproteinase Meprin β.
abstract: 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.
authors.affiliation: Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Barry Lee
authors.initials: BL
authors.lastname: Martin
authors.affiliation: Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Sabena Michelle
authors.initials: SM
authors.lastname: Conley
authors.affiliation: Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Regine Simone
authors.initials: RS
authors.lastname: Harris
authors.affiliation: Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Corshe Devon
authors.initials: CD
authors.lastname: Stanley
authors.affiliation: Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Jean-Marie Vianney
authors.identifier: 0000-0003-1766-9117
authors.initials: JM
authors.lastname: Niyitegeka
authors.affiliation: Department of Biology, North Carolina A&T State University, Greensboro, NC 27411, USA.
authors.forename: Elimelda Moige
authors.identifier: 0000-0002-2963-4379
authors.initials: EM
authors.lastname: Ongeri