Biochemical and histochemical analyses of lecithin:retinol acyltransferase from polar bear (Ursus maritimus) livers
- 46 Downloads
Vitamin A is a fat-soluble vitamin required for many physiological functions. It is known that polar bears (Ursus maritimus) store a large amount of vitamin A within hepatic stellate cells (HSCs). However, the molecular mechanisms for high-capacity storage of vitamin A by polar bear HSCs are unknown. We biochemically and histochemically analyzed lecithin:retinol acyltransferase (LRAT), an enzyme responsible for conversion of retinol to its storage form, retinylesters, in the liver. Surprisingly, LRAT activities of the liver microsome fractions from polar bears weighing 100–500 kg were considerably lower than those obtained from rats (Rattus norvegicus). Although there is a possibility that the quality of polar bear liver specimens was reduced during transport, intrinsic LRAT activity of polar bears might actually be lower than those of other mammals. Fluorescent immunohistochemistry revealed that LRAT and cellular retinol-binding protein (CRBP) I were well co-localized within the liver lobules of polar bears. Taking into account that retinol bound to CRBP I is prevented from degradation and becomes a good substrate of LRAT, we hypothesized that CRBP I effectively conveys retinol to the LRAT, thereby circumventing the low enzymatic activity of LRAT in polar bear livers. As the top predator in the Arctic, polar bears have access to large amounts of vitamin A via the food web. We suggest that polar bears acquired an efficient mechanism of esterification of vitamin A within the liver during the course of their evolution.
KeywordsVitamin A Lecithin:retinol acyltransferase Cellular retinol-binding protein Polar bear Liver Hepatic stellate cell
The authors are grateful to Dr. Trond Berg (Department of Biology, University of Oslo) for his help and encouragement throughout the work. We also thank Misako Shirai for immunohistochemistry and Kiwamu Yoshikawa for vitamin A quantification. This work was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities 2011–2015, JSPS KAKENHI (24255003, 25504001, 16K00872) and the Jikei University Graduate Research Fund.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.
- Miura S, Gan JW, Brzostowski J, Parisi MJ, Schultz CJ, Londos C, Oliver B, Kimmel AR (2002) Functional conservation for lipid storage droplet association among Perilipin, ADRP, and TIP47 (PAT)-related proteins in mammals, drosophila, and dictyostelium. J Biol Chem 277:32253–32257CrossRefPubMedGoogle Scholar
- Nagatsuma K, Hayashi Y, Hano H, Sagara H, Murakami K, Saito M, Masaki T, Lu T, Tanaka M, Enzan H, Aizawa Y, Tajiri H, Matsuura T (2009) Lecithin:retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver. Liver Int 29:47–54CrossRefPubMedGoogle Scholar
- Nagatsuma K, Hano H, Murakami K, Shindo D, Matsumoto Y, Mitobe J, Tanaka K, Saito M, Maehashi H, Owada M, Ikegami M, Tsubota A, Ohkusa T, Aizawa Y, Takagi I, Tajiri H, Matsuura T (2014) Hepatic stellate cells that coexpress LRAT and CRBP-1 partially contribute to portal fibrogenesis in patients with human viral hepatitis. Liver Int 34:243–252CrossRefPubMedGoogle Scholar