|
|||||
|
|
Bioactive TGF-β can associate with lipoproteins and is enriched in those containing apolipoprotein E3 |
|
| Authors: | Ina Tesseur Hui Zhang Walter Brecht† Jacob Corn† Jian-Sheng Gong‡ Katsuhiko Yanagisawa‡ Makoto Michikawa‡ Karl Weisgraber† Yadong Huang† Tony Wyss-Coray§ |
| Institution: | Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA; Gladstone Institute of Neurological Disease, University of California San Francisco, San Francisco, California, USA; Department of Alzheimer's Disease Research, National Institute for Longevity Research, Aichi, Japan; Geriatric Research, Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, California, USA |
| Abstract: | Transforming growth factor-β1 (TGF-β1) has central functions in development, tissue maintenance, and repair and has been implicated in major diseases. We discovered that TGF-β1 contains several amphipathic helices and hydrophobic domains similar to apolipoprotein E (apoE), a protein involved in lipoprotein metabolism. Indeed, TGF-β1 associates with lipoproteins isolated from human plasma, cultured liver cells, or astrocytes, and its bioactivity was highest in high-density lipoprotein preparations. Importantly, lipoproteins containing the apoE3 isoform had higher TGF-β levels and bioactivity than those containing apoE4, a major genetic risk factor for atherosclerosis and Alzheimer's disease. Because TGF-β1 can be protective in these diseases an association with apoE3 may be beneficial. Association of TGF-β with different types of lipoproteins may facilitate its diffusion, regulate signaling, and offer additional specificity for this important growth factor. |
| Keywords: | Alzheimer's disease apolipoprotein E lipoprotein neuroprotective transforming growth factor-β |