ArticleMolecular biology reports1999
Manipulation of the ubiquitin-proteasome pathway in cachexia: pentoxifylline suppresses the activation of 20S and 26S proteasomes in muscles from tumor-bearing rats.
Article in Molecular biology reports, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 78 citations in OpenAlex.
- Blocking muscle wasting via deletion of the muscle-specific E3 ligase MuRF1 impedes pancreatic tumor growth.Communications biology · 2023Article
- Blocking muscle wasting via deletion of the muscle-specific E3 ubiquitin ligase MuRF1 impedes pancreatic tumor growth.Research square · 2023Article
- Repurposing of Antibiotic Sulfisoxazole Inhibits Lipolysis in Pre-Clinical Model of Cancer-Associated Cachexia.Biology · 2021Article
- Muscle alterations in the development and progression of cancer-induced muscle atrophy: a review.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Review
- mTOR and Tumor Cachexia.International journal of molecular sciences · 2018Review
- Molecular pathways leading to loss of skeletal muscle mass in cancer cachexia--can findings from animal models be translated to humans?BMC cancer · 2016Review
- F-BOX proteins in cancer cachexia and muscle wasting: Emerging regulators and therapeutic opportunities.Seminars in cancer biology · 2016Review
- The proteasome inhibitor MG132 reduces immobilization-induced skeletal muscle atrophy in mice.BMC musculoskeletal disorders · 2011Article
- The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the Apc(Min/+) mouse.PloS one · 2011Article
- Roles and potential therapeutic targets of the ubiquitin proteasome system in muscle wasting.BMC biochemistry · 2007Review
- Induction of protein catabolism in myotubes by 15(S)-hydroxyeicosatetraenoic acid through increased expression of the ubiquitin-proteasome pathway.British journal of cancer · 2003Article
- Increased muscle proteasome activity correlates with disease severity in gastric cancer patients.Annals of surgery · 2003Article
- Torbafylline (HWA 448) inhibits enhanced skeletal muscle ubiquitin-proteasome-dependent proteolysis in cancer and septic rats.The Biochemical journal · 2002Article
- Identification of cathepsin L as a differentially expressed message associated with skeletal muscle wasting.The Biochemical journal · 2001Article
- Adaptation of the ubiquitin-proteasome proteolytic pathway in cancer cachexia.Molecular biology reports · 1999Review
- Proteolysis in illness-associated skeletal muscle atrophy: from pathways to networks.Critical reviews in clinical laboratory sciencesReview
- Understanding the Role of Exercise in Cancer Cachexia Therapy.American journal of lifestyle medicineArticle
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of pharmacological approaches for preventing the loss of muscle proteins would be extremely valuable for cachectic patients. For example, severe wasting in cancer patients correlates with a reduced efficacy of chemotherapy and radiotherapy. Pentoxifylline (PTX) is a very inexpensive xanthine derivative, which is widely used in humans as a haemorheological agent, and inhibits tumor necrosis factor transcription. We have shown here that a daily administration of PTX prevents muscle atrophy and suppresses increased protein breakdown in Yoshida sarcoma-bearing rats by inhibiting the activation of a nonlysosomal, Ca(2+)-independent proteolytic pathway. PTX blocked the ubiquitin pathway, apparently by suppressing the enhanced expression of ubiquitin, the 14-kDa ubiquitin conjugating enzyme E2, and the C2 20S proteasome subunit in muscle from cancer rats. The 19S complex and 11S regulator associate with the 20S proteasome and regulate its peptidase activities. The mRNA levels for the ATPase subunit MSS1 of the 19S complex increased in cancer cachexia, in contrast with mRNAs of other regulatory subunits. This adaptation was suppressed by PTX, suggesting that the drug inhibited the activation of the 26S proteasome. This is the first demonstration of a pharmacological manipulation of the ubiquitin-proteasome pathway in cachexia with a drug which is well tolerated in humans. Overall, the data suggest that PTX can prevent muscle wasting in situations where tumor necrosis factor production rises, including cancer, sepsis, AIDS and trauma.
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