Gross, Simon and Danielyan, Lusine and Buechler, Christa and Kubitza, Marion and Klein, Kathrin and Schwab, Matthias and Melter, Michael and Weiss, Thomas S. (2024) Hepatic Amyloid Beta-42-Metabolizing Proteins in Liver Steatosis and Metabolic Dysfunction-Associated Steatohepatitis. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 25 (16): 8768. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Amyloid beta (A beta) plays a major role in the pathogenesis of Alzheimer's disease and, more recently, has been shown to protect against liver fibrosis. Therefore, we studied A beta-42 levels and the expression of genes involved in the generation, degradation, and transport of A beta proteins in liver samples from patients at different stages of metabolic dysfunction-associated liver disease (MASLD) and under steatotic conditions in vitro/in vivo. Amyloid precursor protein (APP), key A beta-metabolizing proteins, and A beta-42 were analyzed using RT-PCR, Western blotting, Luminex analysis in steatotic in vitro and fatty liver mouse models, and TaqMan qRT-PCR analysis in hepatic samples from patients with MASLD. Hepatocytes loaded with palmitic acid induced APP, presenilin, and neprilysin (NEP) expression, which was reversed by oleic acid. Increased APP and NEP, decreased BACE1, and unchanged A beta-42 protein levels were found in the steatotic mouse liver compared to the normal liver. A beta-42 concentrations were low in MASLD samples of patients with moderate to severe fibrosis compared to the livers of patients with mild or no MASLD. Consistent with the reduced A beta-42 levels, the mRNA expression of proteins involved in APP degradation (ADAM9/10/17, BACE2) and A beta-42 cleavage (MMP2/7/9, ACE) was increased. In the steatotic liver, the expression of APP- and A beta-metabolizing proteins is increased, most likely related to oxidative stress, but does not affect hepatic A beta-42 levels. Consistent with our previous findings, low A beta-42 levels in patients with liver fibrosis appear to be caused by the reduced production and enhanced non-amyloidogenic processing of APP.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BETA-SECRETASE; OXIDATIVE STRESS; EXPRESSION; DISEASE; MODEL; BIOLOGY; TARGET; CELLS; MASLD; NAFLD; MASH; NASH; steatosis; fibrosis; oxidative stress; fatty acids; amyloid |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Jul 2025 11:26 |
| Last Modified: | 28 Jul 2025 11:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/63858 |
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