albumin - publications

Predict more albumin - ligand interactions now!


1. J Neuroinflammation. 2012 Apr 16;9(1):68. [Epub ahead of print]

Albumin induces upregulation of matrix metalloproteinase-9 in astrocytes via MAPK
and reactive oxygen species-dependent pathways.

Ralay Ranaivo H, Hodge JN, Choi N, Wainwright MS.

ABSTRACT: BACKGROUND: Astrocytes are an integral component of the blood-brain
barrier (BBB) which may be compromised by ischemic or traumatic brain injury. In
response to trauma, astrocytes increase expression of the endopeptidase matrix
metalloproteinase (MMP)-9. Compromise of the BBB leads to the infiltration of
fluid and blood-derived proteins including albumin into the brain parenchyma.
Albumin has been previously shown to activate astrocytes and induce the
production of inflammatory mediators. The effect of albumin on MMP-9 activation
in astrocytes is not known. We investigated the molecular mechanisms underlying
the production of MMP-9 by albumin in astrocytes. METHODS: Primary enriched
astrocyte cultures were used to investigate the effects of exposure to albumin on
the release of MMP-9. MMP-9 expression was analyzed by zymography. The
involvement of mitogen-activated protein kinase (MAPK), reactive oxygen species
(ROS) and the TGF-beta receptor-dependent pathways were investigated using
pharmacological inhibitors. The production of ROS was observed by
dichlorodihydrofluorescein diacetate fluorescence. The level of the MMP-9
inhibitor tissue inhibitor of metalloproteinase (TIMP)-1 produced by astrocytes
was measured by ELISA. RESULTS: We found that albumin induces a time-dependent
release of MMP-9 via the activation of p38 MAPK and extracellular signal
regulated kinase, but not Jun kinase. Albumin-induced MMP-9 production also
involves ROS production upstream of the MAPK pathways. However, albumin-induced
increase in MMP-9 is independent of the TGF-beta receptor, previously described
as a receptor for albumin. Albumin also induces an increase in TIMP-1 via an
undetermined mechanism. CONCLUSIONS: These results link albumin (acting through
ROS and the p38 MAPK) to the activation of MMP-9 in astrocytes. Numerous studies
identify a role for MMP-9 in the mechanisms of compromise of the BBB,
epileptogenesis, or synaptic remodeling after ischemia or traumatic brain injury.
The increase in MMP-9 produced by albumin further implicates both astrocytes and
albumin in the acute and long-term complications of acute CNS insults, including
cerebral edema and epilepsy.

PMID: 22507553 [PubMed - as supplied by publisher]