[show abstract][hide abstract] ABSTRACT: Changes in matrix metalloproteinase (MMP) activities would contribute to the accumulation of extracellular matrix during acute kidney allograft rejection. MMP-2 and MMP-9 and other gelatinolytic activities were examined in the rejected graft and the urine of a rat model of acute kidney rejection (orthotopic allotransplantation from a Buffalo donor to a Wistar-Furth recipient) by either zymography or fluorescence assay. MMP-2, membrane type 1 (MT1)-MMP, and tissue inhibitor of metalloproteinase (TIMP)-2 were also examined by immunodetection. The proMMP-2 activity and protein level increased in the graft during rejection when compared with normal Buffalo kidney, whereas activated MMP-2 decreased. TIMP-2 protein levels were markedly decreased and MT1-MMP proteolytic fragments (44-40 kDa) were undetectable. This suggests an altered MT1-MMP-dependent processing of proMMP-2 into active MMP-2 due to a diminished TIMP-2 level in acute kidney rejection. In the urine the overall gelatinolytic activity decreased considerably, although activity associated with an as yet unidentified 78-kDa protein appeared 6 days after transplantation.
Transplant International 05/2003; 16(4):262-9. · 3.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: 1. The blood-brain barrier (BBB) contributes to brain homeostastis and fulfills a protective function by controlling the access of solutes and toxic substances to the central nervous system (CNS). The efflux transporter P-glycoprotein (P-gp) is a key element of the molecular machinery that confers special permeability properties to the BBB. 2. P-gp, which was initially recognized for its ability to expel anticancer drugs from multidrug-resistant cancer cells, is strongly expressed in brain capillaries. Its expression in the BBB limits the accumulation of many hydrophobic molecules and potentially toxic substances in the brain. 3. The purpose of this review is to summarize the current state of knowledge about the expression of P-gp, its cellular localization as well as its possible functions in the BBB.