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http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum
Investigative Ophthalmology and Visual Science. 2008 May 30.
The trefoil factor TFF1 protects conjunctival cells from apoptosis at pre and post-mitochondrial levels.
Buron N, Guery L, Creuzot-Garcher C, Lafontaine PO, Bron A, Rio MC, Solary E.
University of Burgundy, Inserm UMR 866, Dijon, France.
PURPOSE. Goblet cells of the conjunctival epithelium synthesize and secrete TFF1 (Trefoil factor 1), a small protease-resistant peptide which, together with mucins, is responsible for the rheologic properties of the tear film. This study aimed to determine whether TFF1, whose synthesis increases in inflammatory conditions such as pterygium, could protect conjunctival cells from apoptosis.
METHODS. Chang conjunctival cells, either wild-type or expressing TFF1 through stable transfection, were exposed to benzalkonium chloride (BAC) and ultraviolet irradiation (UV) to trigger their apoptosis. We used cell fractionation to detect lipid raft-associated proteins, co-immunoprecipitation to explore the formation of a death-inducing signalling complex (DISC) and a combination of immunofluorescence, immunoblotting, flow cytometry, siRNA-mediated decrease in gene expression and electrophoretic mobility shift assay to explore the mechanisms of TFF1 protective effects.
RESULTS. TFF1 protects Chang conjunctival cells from apoptosis induced by UV irradiation and BAC at two levels. First, TFF1 prevents caspase-8 activation at the level of the DISC that involves Fas receptor in plasma membrane rafts, which in turn decreases the mitochondrial release of cytochrome c. Secondly, TFF1 interferes with caspase-9 and caspase-3 activation through NF-kappaB induced increase in the expression of XIAP (X-linked Inhibitor of Apoptosis Protein).
CONCLUSIONS. TFF1 up-regulation upon inflammatory conditions may be a protective mechanism that limits conjunctival cell loss by inhibiting apoptosis both upstream and downstream of the mitochondrial events. These observations suggest a potential interest of TFF1 or related peptides to prevent cell death in ocular surface disorders.
PMID: 18515572 [PubMed - as supplied by publisher]
http://en.wikipedia.org/wiki/Trefoil_factor_1
Investigative Ophthalmology and Visual Science. 2008 May 30.
The trefoil factor TFF1 protects conjunctival cells from apoptosis at pre and post-mitochondrial levels.
Buron N, Guery L, Creuzot-Garcher C, Lafontaine PO, Bron A, Rio MC, Solary E.
University of Burgundy, Inserm UMR 866, Dijon, France.
PURPOSE. Goblet cells of the conjunctival epithelium synthesize and secrete TFF1 (Trefoil factor 1), a small protease-resistant peptide which, together with mucins, is responsible for the rheologic properties of the tear film. This study aimed to determine whether TFF1, whose synthesis increases in inflammatory conditions such as pterygium, could protect conjunctival cells from apoptosis.
METHODS. Chang conjunctival cells, either wild-type or expressing TFF1 through stable transfection, were exposed to benzalkonium chloride (BAC) and ultraviolet irradiation (UV) to trigger their apoptosis. We used cell fractionation to detect lipid raft-associated proteins, co-immunoprecipitation to explore the formation of a death-inducing signalling complex (DISC) and a combination of immunofluorescence, immunoblotting, flow cytometry, siRNA-mediated decrease in gene expression and electrophoretic mobility shift assay to explore the mechanisms of TFF1 protective effects.
RESULTS. TFF1 protects Chang conjunctival cells from apoptosis induced by UV irradiation and BAC at two levels. First, TFF1 prevents caspase-8 activation at the level of the DISC that involves Fas receptor in plasma membrane rafts, which in turn decreases the mitochondrial release of cytochrome c. Secondly, TFF1 interferes with caspase-9 and caspase-3 activation through NF-kappaB induced increase in the expression of XIAP (X-linked Inhibitor of Apoptosis Protein).
CONCLUSIONS. TFF1 up-regulation upon inflammatory conditions may be a protective mechanism that limits conjunctival cell loss by inhibiting apoptosis both upstream and downstream of the mitochondrial events. These observations suggest a potential interest of TFF1 or related peptides to prevent cell death in ocular surface disorders.
PMID: 18515572 [PubMed - as supplied by publisher]
http://en.wikipedia.org/wiki/Trefoil_factor_1
Trefoil factor 1, also known as TFF1, is a human gene.[1]
Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer, and affect healing of the epithelium. This gene, which is expressed in the gastric mucosa, has also been studied because of its expression in human tumors. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.[1]
Members of the trefoil family are characterized by having at least one copy of the trefoil motif, a 40-amino acid domain that contains three conserved disulfides. They are stable secretory proteins expressed in gastrointestinal mucosa. Their functions are not defined, but they may protect the mucosa from insults, stabilize the mucus layer, and affect healing of the epithelium. This gene, which is expressed in the gastric mucosa, has also been studied because of its expression in human tumors. This gene and two other related trefoil family member genes are found in a cluster on chromosome 21.[1]