department of pharmacology

Johannes von Lintig, Ph.D.

Johannes von Lintig

Associate Professor with Tenure, Pharmacology

Phone: (216) 368-3528
Fax: (216) 368-1300
E-mail: Johannes.vonlintig@case.edu
W341

Research

Carotenoids affect a rich variety of physiological functions in nature and are beneficial for human health, serving as antioxidants in lipophilic environments and blue light filters in the macula of the human retina. ABB JournalThese dietary compounds also are the natural precursors for retinoids (vitamin A and its derivatives) that play critical roles for vision and gene regulation. To establish and sustain retinoid-dependent physiological processes, these compounds must be absorbed in the intestine, transported in the body, metabolized to biologically active compounds such as 11-cis-retinal and all-trans-retinoic acid. Vitamin A deficiency is still a major health problem in developing countries. Moreover, mutations of genes encoding the involved components have emerged as important causes for not only blinding diseases but also fatal diseases such as the Matthew-Wood syndrome, characterized by pleiotropic, multisystem malformations that include cardiac deformities and ocular defects. Although knowledge about retinoid biology has significantly increased, many aspects remain poorly understood, including the metabolism of retinoids’ parent precursors the carotenoids.


Our laboratory has molecularly identified and biochemically characterized key players of carotenoid metabolism, including the vitamin A forming enzyme. Cell MagazineOur approaches include structure-function analysis of these proteins, studies cell culture models, and the establishment of disease-relevant animal models for the analysis of the consequences of their loss of function. Further, we are addressing the question how the supply of carotenoids and retinoids to tissues is regulated to avoid excess and deficiency, which both can have deleterious consequences and can cause disease. Additionally, we are working on questions concerning ocular retinoid metabolism and the putative role of retinoids in retinal damage. We hope that our research will contribute to a better molecular and mechanistic understanding of carotenoid and retinoid metabolism in health and disease.

Selected Publications:

Lobo, G.P., Amengual, J., Li, H.N.M., Golczak, M., Palczewski, K.,von Lintig , J. (2010) β,β-Carotene Decreases PPAR γ activity and reduces lipid storage capacity of adipocytes in a BCMO1-dependent manner. J. Biol. Chem. 285(36):27891-2789.

Lobo, G.P., Hessel, S., Eichinger, A., Noy, N., Moise, A.R., Wyss, A., Palczewski, K. and von Lintig, J. (2010) ISX is a retinoic acid-sensitive gatekeeper that controls intestinal {beta},{beta}-carotene absorption and vitamin A production. FASEB J. 24(6):1656-1666.

Wang, X., Wang, T., Jiao, Y., von Lintig, J. and Montell, C.* (2010) Requirement for an enzymatic visual cycle in Drosophila. Curr Biol. 20:93-102. *Dispatch in the same issue

Voolstra, O., Oberhauser, V., Sumser, E., Meyer, N.E., Maguire, M.E., Huber, A. and von Lintig J. (2010) NinaB is essential for Drosophila vision but induces retinal degeneration in opsin-deficient photoreceptors. J. Biol. Chem. 285:2130-2139.

Oberhauser, V., Voolstra, O., Bangert, A., von Lintig, J. and Vogt K. (2008) NinaB combines carotenoid oxygenase and retinoid isomerase in a single polypeptide. Proc. Natl. Sci. U.S.A. 105:19000-5.

Isken, A., Golczak, M., Oberhauser, V., Hunzelmann, S., Driever, W., Imanishi, Y., Palczewski K., von Lintig, J.* (2008) RBP4 disrupts vitamin A uptake homeostasis in a STRA6-deficient animal model for Matthew-Wood syndrome. Cell Metabolism. (3):258-68. *Cover story

Hessel, S., Eichinger, A., Isken, A., Huntzelmann, S., Hunziker, W., Goralczyk, R., Oberhauser, V. von Lintig, J. and Wyss, A. (2007) CMO1 deficiency abolishes vitamin A production from beta-carotene and alters lipid metabolism in mice. J. Biol. Chem. 282:33553-33561.

Isken, A., Holzschuh, J., Fischer, L., Lampert, J.M., Oberhauser, V., Palczewski, K. and von Lintig, J. (2007) Sequestration of retinyl esters is essential for retinoid-signaling in the zebrafish embryo. J. Biol. Chem. 282:1144-11451.

Wenzel, A., Oberhauser, V., Pugh, E.N. Jr, Lamb, T.D., Grimm, C., Samardzija, M., Fahl, E., Seeliger, M.W., Reme, C.E., and von Lintig, J. (2005) The retinal G protein-coupled receptor (RGR) enhances isomerohydrolase activity independent of light. J. Biol. Chem. 280:29874-84.

Lampert, J.M., Holzschuh, J., Hessel., S., Driever, W., Vogt, K., and von Lintig, J. (2003) Provitamin A conversion to retinal via the beta-carotene-oxygenase is essential for pattern formation and differentiation during zebrafish development. Development 130: 2173-86.

Kiefer, C., Sumser, E., Wernet M.F. and von Lintig, J. (2002) A class B scavenger receptor mediates the cellular uptake of carotenoids in Drosophila. Proc. Natl. Acad. Sci. U. S. A. 99: 10581-6.

Kiefer, C., Hessel, S., Lampert, J., Vogt, K., Lederer, M.O., Breithaupt, D.E. and von Lintig, J. (2001) Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A. J. Biol. Chem. 276: 14110-6.

von Lintig, J. Dreher, A., Kiefer, C., Wernet, M.F., and Vogt, K. (2001) Analysis of the blind Drosophila mutant ninaB identifies gene encoding the key enzyme for vitamin A formation in vivo. Proc. Natl. Acad. Sci. U.S.A. 98: 1130-5.

von Lintig J., and Vogt K. (2000) Filling the gap in vitamin A research: Molecular Identification of an enzyme cleaving beta-carotene to retinal J. Biol. Chem. 275: 11915-20 (Editors' Choice: Highlights of the recent literature. Science 288: 931).