Endocrine Abstracts (2002) 3 OC45

Evidence for a role of the ATP-binding cassette transporter - A1 (ABC-A1) in the externalisation of annexin I from folliculostellate cells

MJ Epton1, LP Chapman1, JF Morris1, JC Buckingham2 & HC Christian1

1Department of Human Anatomy and Genetics, University of Oxford, Oxford, UK; 2Department of Neuroendocrinology, Faculty of Medicine, Imperial College, London, UK.

Annexin I (ANXA1), a Ca2+- and phospholipid-binding protein is an important mediator of glucocorticoid (GC) action in the host defence and neuroendocrine systems. In the anterior pituitary ANXA1 is highly expressed by the folliculo-stellate (FS) cells (1). We have shown that GCs cause the externalization of annexin I in a FS cell line (murine TtT/GF) despite the fact that ANXA1 lacks a signal sequence and is not packaged in secretory granules. In bacteria and yeast ABC transporters are involved in the secretion of secretory proteins that lack a signal sequence. ABC-A1, a subtype present in mammalian cells, is involved in the secretion of interleukin 1 beta, a powerful mediator of inflammation, which also lacks a signal sequence (2). We therefore investigated the role of ABC-A1 in ANXA1 externalisation by testing the effects of a known inhibitor of ABC-A1, the sulphonylurea glyburide (currently used in the oral therapy of non-insulin dependent diabetes) on the GC-induced externalization of ANXA1 from (a) TtT/GF cells and (b) mouse anterior pituitary tissue by use of Western blot and immunofluorescence analysis. Glyburide (100 microM; 3h) significantly (P>0.01) inhibited the externalization of ANXA1 induced by dexamethasone (0.1 microM; 3h) in both TtT/GF cells and anterior pituitary tissue. We have also shown that both TtT/GF cells and mouse anterior pituitary express ABC-A1 mRNA and protein by RT-PCR and Western blot respectively. These findings indicate a role for ABC-A1 in the secretion of annexin I by FS cells.

(1) Traverso V, Christian HC, Morris JF, Buckingham JC 1999 Endocrinology 140: 4311-4319.

(2) Hamon Y, Luciani MF, Becq F, Verrier B, Rubartelli A, Chimini, G 1997 Blood 90: 2911-5

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