Journal
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
Volume 504, Issue 1, Pages 3-10Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2010.05.010
Keywords
Vitamin A; Carotenoid; Carotene cleavage; Chylomicron; Diet
Categories
Funding
- Fulbright Faculty Development Program
- National Institutes of Health [R01 DK068347, R01 DK079221, R01 DK044498, R01 HL049879, R01 HD042174]
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Hepatic stellate cells (HSCs) are responsible for storing 90-95% of the retinoid present in the liver. These cells have been reported in the literature also to accumulate dietary p-carotene, but the ability of HSCs to metabolize beta-carotene in situ has not been explored. To gain understanding of this, we investigated whether beta-carotene-15,15'-monooxygensase (Bcmo1) and beta-carotene-9',10'-monooxygenase (Bcmo2) are expressed in HSCs. Using primary HSCs and hepatocytes purified from wild type and Bcmo1-deficient mice, we establish that Bcmo1 is highly expressed in HSCs; whereas Bcmo2 is expressed primarily in hepatocytes. We also confirmed that HSCs are an important cellular site within the liver for accumulation of dietary p-carotene. Bcmo2 expression was found to be significantly elevated for livers and hepatocytes isolated from Bcmo1-deficient compared to wild type mice. This elevation in Bcmo2 expression was accompanied by a statistically significant increase in hepatic apo-12'-carotenal levels of Bcmo1-deficient mice. Although apo-10'-carotenal, like apo-12'-carotenal, was readily detectable in livers and serum from both wild type and Bcmo1-deficient mice, we were unable to detect either apo-8'- or apo-14'-carotenals in livers or serum from the two strains. We further observed that hepatic triglyceride levels were significantly elevated in livers of Banal-deficient mice fed a beta-carotene-containing diet compared to mice receiving no p-carotene. Collectively, our data establish that HSCs are an important cellular site for p-carotene accumulation and metabolism within the liver. (C) 2010 Elsevier Inc. All rights reserved.
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