PMID- 2295699 OWN - NLM STAT- MEDLINE DCOM- 19900214 LR - 20220330 IS - 0021-9738 (Print) IS - 0021-9738 (Linking) VI - 85 IP - 1 DP - 1990 Jan TI - Tumor necrosis factor-alpha inhibits albumin gene expression in a murine model of cachexia. PG - 248-55 AB - The mechanisms responsible for decreased serum albumin levels in patients with cachexia-associated infection, inflammation, and cancer are unknown. Since tumor necrosis factor-alpha (TNF alpha) is elevated in cachexia-associated diseases, and chronic administration of TNF alpha induces cachexia in animal models, we assessed the regulation of albumin gene expression by TNF alpha in vivo. In this animal model of cachexia, Chinese hamster ovary cells transfected with the functional gene for human TNF alpha were inoculated into nude mice (TNF alpha mice). TNF alpha mice became cachectic and manifested decreased serum albumin levels, albumin synthesis, and albumin mRNA levels. However, even before the TNF alpha mice lost weight, their albumin mRNA steady-state levels were decreased approximately 90%, and in situ hybridization revealed a low level of albumin gene expression throughout the hepatic lobule. The mRNA levels of several other genes were unchanged. Hepatic nuclei from TNF alpha mice before the onset of weight loss were markedly less active in transcribing the albumin gene than hepatic nuclei from control mice. Therefore, TNF alpha selectively inhibits the genetic expression of albumin in this model before weight loss. FAU - Brenner, D A AU - Brenner DA AD - Department of Medicine, University of California, San Diego 92093. FAU - Buck, M AU - Buck M FAU - Feitelberg, S P AU - Feitelberg SP FAU - Chojkier, M AU - Chojkier M LA - eng GR - DK07202/DK/NIDDK NIH HHS/United States GR - DK38652/DK/NIDDK NIH HHS/United States GR - GM41804/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Clin Invest JT - The Journal of clinical investigation JID - 7802877 RN - 0 (RNA, Messenger) RN - 0 (Serum Albumin) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Animals MH - Blotting, Northern MH - Cachexia/etiology/*physiopathology MH - Cell Line MH - Cell Nucleus/metabolism MH - Disease Models, Animal MH - *Gene Expression MH - *Genes MH - Humans MH - Liver/metabolism MH - Mice MH - Mice, Nude MH - Nucleic Acid Hybridization MH - RNA, Messenger/genetics MH - Serum Albumin/biosynthesis/*genetics MH - Transcription, Genetic MH - Transfection MH - Tumor Necrosis Factor-alpha/genetics/*physiology PMC - PMC296412 EDAT- 1990/01/01 00:00 MHDA- 1990/01/01 00:01 PMCR- 1990/01/01 CRDT- 1990/01/01 00:00 PHST- 1990/01/01 00:00 [pubmed] PHST- 1990/01/01 00:01 [medline] PHST- 1990/01/01 00:00 [entrez] PHST- 1990/01/01 00:00 [pmc-release] AID - 10.1172/JCI114419 [doi] PST - ppublish SO - J Clin Invest. 1990 Jan;85(1):248-55. doi: 10.1172/JCI114419.