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HEME CARRIER PROTEIN 1 (HCP1) IS EXPRESSED IN A pH DEPENDANT MANNER IN THE HUMAN GASTROINTESTINAL TRACT
J Patel1, BL Urquhart2, JC Gregor3, N Chande3, RB Kim2
1Department of Medicine; 2Division of Clinical Pharmacology, Department of Medicine; 3Division of Gastroenterology, Department of Medicine, Schulich School of Medicine & Dentistry at the University of Western Ontario
Heme Carrier Protein 1 (HCP1) was initially discovered as an intestinal protein responsible for heme absorption. However, this protein has recently been shown to be a proton coupled intestinal folate uptake transporter. As HCP1 is a mediator of intestinal folate uptake, it may be an important determinant of folate homeostasis.
The aim of our study is to characterize the longitudinal expression of HCP1 in the gastrointestinal tract. As HCP1 mediates proton coupled folate transport, it is our hypothesis that proximal intestine (i.e. duodenum, pH ~ 5.5-6.0) will exhibit high HCP1 expression whereas more distal sections such as the terminal ileum and colon (pH ~ 7.4) will display reduced expression.
Two additional pinch biopsies were collected from the duodenum, terminal ileum and colon of patients undergoing diagnostic upper endoscopy and colonoscopy. These samples were analyzed for protein expression by Western blot. To assess between mRNA and protein expression in the gastrointestinal biopsy samples, HCP1 mRNA expression is also being assessed using quantitative RT-PCR.
Preliminary evidence from Western blot analysis supports our hypothesis with respect to protein expression, showing increased expression of HCP1 in duodenal biopsies, with decreasing levels expressed in biopsies from the distal gastrointestinal tract (terminal ileum and colon). Quantitative RT-PCR for analysis of HCP1 mRNA is currently in process.
In summary, recent studies have shown that HCP1 is a major mediator of intestinal folate uptake and that this process is pH-dependent. Our current data suggest that the pattern HCP1 expression is also dependent on regional intestinal pH, with highest expression seen in the proximal intestine. In addition, cancer tissue proliferation is often dependent on folate, thus HCP1 may turn out to be a molecular target for chemotherapeutic agents as well as folate antagonists. Accordingly, our findings shed important new information regarding the regional expression of HCP1 in the intestine and suggest this transporter may be crucial to the absorption and pharmacological action of folate and folate antagonists in clinical use.