The autophagic-lysosomal and ubiquitin proteasome systems are simultaneously activated in the skeletal muscle of gastric cancer patients with cachexia.

التفاصيل البيبلوغرافية
العنوان:	The autophagic-lysosomal and ubiquitin proteasome systems are simultaneously activated in the skeletal muscle of gastric cancer patients with cachexia.
المؤلفون:	Zhang Y; Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.; Department of Cardiothoracic Surgery, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu Province, China., Wang J; Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China., Wang X; Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China., Gao T; Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China., Tian H; Department of General Surgery, Jinling Hospital Affiliated to Southern Medical University, Nanjing, Jiangsu Province, China., Zhou D; Department of General Surgery, Jinling Hospital Affiliated to Southern Medical University, Nanjing, Jiangsu Province, China., Zhang L; Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China., Li G; Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China., Wang X; Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.
المصدر:	The American journal of clinical nutrition [Am J Clin Nutr] 2020 Mar 01; Vol. 111 (3), pp. 570-579.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Elsevier Country of Publication: United States NLM ID: 0376027 Publication Model: Print Cited Medium: Internet ISSN: 1938-3207 (Electronic) Linking ISSN: 00029165 NLM ISO Abbreviation: Am J Clin Nutr Subsets: MEDLINE
أسماء مطبوعة:	Publication: 2023- : [New York, NY] : Elsevier Original Publication: Bethesda, MD : American Society of Clinical Nutrition
مواضيع طبية MeSH:	Autophagy, Cachexia/enzymology , Lysosomes/metabolism , Proteasome Endopeptidase Complex/metabolism , Sarcopenia/enzymology , Stomach Neoplasms/enzymology, Adult ; Aged ; Cachexia/genetics ; Cachexia/pathology ; Cachexia/physiopathology ; Female ; Humans ; Lysosomes/enzymology ; Male ; Middle Aged ; Muscle, Skeletal/cytology ; Muscle, Skeletal/enzymology ; Muscle, Skeletal/pathology ; Proteasome Endopeptidase Complex/genetics ; Sarcopenia/metabolism ; Sarcopenia/pathology ; Sarcopenia/physiopathology ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Stomach Neoplasms/physiopathology ; Ubiquitin/metabolism
مستخلص:	Background: Cancer cachexia is characterized by weight loss, especially ongoing skeletal muscle loss, and is associated with poor patient outcomes. However, the molecular mechanism of skeletal muscle wasting is not fully understood. Objectives: We aimed to investigate muscle fiber morphology and proteolysis system activity changes that may account for cancer cachexia and to relate these changes to patients' clinical phenotypes. Methods: We divided 39 patients with resectable gastric cancer into 4 groups based on the presence of cachexia (weight loss) and/or sarcopenia (low muscularity), including a noncachexia/nonsarcopenia group (N, n = 10), a cachexia/sarcopenia group (CS, n = 13), a cachexia/nonsarcopenia group (C, n = 9), and a noncachexia/sarcopenia group (S, n = 7). Rectus abdominis muscle biopsy specimens were obtained intraoperatively. Muscle fiber size, ultrastructural architecture, and the expression of autophagic-lysosomal system (ALS) and ubiquitin proteasome system (UPS) markers were assayed. Results: Mean ± SD muscle fiber cross-sectional areas were significantly decreased in the CS (460 ± 120 μm2) and S groups (480 ± 135 μm2) compared with the N (1615 ± 388 μm2, both P < 0.05) and C groups (1219 ± 302 μm2, both P < 0.05). In the C, S, and CS groups, the muscle exhibited tissue disorganization and autophagosome formation to different degrees. The levels of ALS and UPS markers were significantly increased in the CS, C, and S groups compared with the N group. Alterations in muscle fiber morphology and increased ALS and UPS activity were related to severe muscle loss, but not weight loss. Conclusions: The ALS and UPS are simultaneously activated in cancer cachexia and may play coordinated roles in cachexia-induced muscle loss. (Copyright © The Author(s) 2020.)
فهرسة مساهمة:	Keywords: autophagy; cancer cachexia; gastric cancer; lysosome; muscle wasting; proteasome; ubiquitin
المشرفين على المادة:	0 (Ubiquitin) EC 3.4.25.1 (Proteasome Endopeptidase Complex)
تواريخ الأحداث:	Date Created: 20200123 Date Completed: 20200505 Latest Revision: 20230214
رمز التحديث:	20231215
DOI:	10.1093/ajcn/nqz347
PMID:	31968072
قاعدة البيانات:	MEDLINE

الوصف
تدمد:	1938-3207
DOI:	10.1093/ajcn/nqz347