Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FOXO1 (forkhead box O1), a forkhead-type transcription factor whose gene expression is up-regulated in the skeletal muscle during starvation, appears to be a key molecule of energy metabolism and skeletal muscle atrophy. Cathepsin L, a lysosomal proteinase whose expression is also up-regulated in the skeletal muscle during starvation, is induced in transgenic mice overexpressing FOXO1 relative to wild-type littermates. In the present study, we conducted in vivo and in vitro experiments focusing on FOXO1 regulation of Ctsl (cathepsin L gene; CTSL1 in humans) expression in the skeletal muscle. During fasting and refeeding of C57BL/6 mice, Ctsl was regulated in parallel with FOXO1 in the skeletal muscle. Fasting-induced Ctsl expression was attenuated in transgenic mice overexpressing a dominant-negative form of FOXO1 or in skeletal-muscle-specific Foxo1-knockout mice relative to respective wild-type controls. Using C2C12 mouse myoblasts overexpressing a constitutively active form of FOXO1, we showed that FOXO1 induces Ctsl expression. Moreover, we found FOXO1-binding sites in both the mouse Ctsl and human CTSL1 promoters. The luciferase reporter analysis revealed that the mouse Ctsl and human CTSL1 promoters are activated by FOXO1, which is abolished by mutations in the consensus FOXO1-binding sites. Gel mobility-shift and chromatin immunoprecipiation assays showed that FOXO1 is recruited and binds to the Ctsl promoter. The present study provides in vivo and in vitro evidence that Ctsl is a direct target of FOXO1 in the skeletal muscle, thereby suggesting a role for the FOXO1/cathepsin L pathway in fasting-induced skeletal muscle metabolic change and atrophy.
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PMID:The cathepsin L gene is a direct target of FOXO1 in skeletal muscle. 2008 26

We isolated a homolog of cathepsin L from a cDNA library of the olive flounder liver. The flounder cathepsin L1 transcript consisted of 1,221 bp that encoded a polypeptide of 334 amino acids. The overall identity between flounder cathepsin L1 and other cathepsin Ls was 50-64%, and flounder cathepsin L1 contained the highly conserved ERFNIN-motif. A phylogenetic tree indicated that flounder cathepsin L1 is in the same monophyletic group as zebrafish cathepsin Lc. RT-PCR analysis revealed that cathepsin L1 transcripts were expressed only in the liver. They were detected from 28 d post-hatching. Under starvation conditions, cathepsin L1 expression was decreased at 30 d.
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PMID:Molecular cloning and mRNA expression of the liver-specific cathepsin L1 gene of the olive flounder, Paralichthys olivaceus. 2167 May 5