Light scattering and sedimentation of native human adult and fetal globin.

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Studies on the relations between molecular and functional properties of hemoglobin. I. The effect of salts on the molecular weight of human hemoglobin.

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Studies on the Relations between Molecular and Functional Properties of Hemoglobin: III. THE INFLUENCE OF SALTS ON THE BOHR EFFECT IN HUMAN HEMOGLOBIN

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STUDIES ON THE OXIDATION-REDUCTION POTENTIALS OF HEME PROTEINS. V. THE OXIDATION BOHR EFFECT IN NORMAL HUMAN HEMOGLOBIN AND HUMAN HEMOGLOBIN DIGESTED WITH CARBOXYPEPTIDASE A.

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Studies on carboxypeptidase digests of human hemoglobin.

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Studies on the Relations between Molecular and Functional Properties of Hemoglobin V. THE INFLUENCE OF TEMPERATURE ON THE BOHR EFFECT IN HUMAN AND IN HORSE HEMOGLOBIN

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STUDIES ON THE OXIDATION-REDUCTION POTENTIALS OF HEME PROTEINS. II. CARBOXYPEPTIDASE DIGESTS OF HUMAN HEMOGLOBIN.

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MuRF-1 and p-GSK3β expression in muscle atrophy of liver cirrhosis

Background: Chronic diseases, including cirrhosis, are often accompanied by protein-energy malnutrition and muscle loss, which in turn negatively affect quality of life, morbidity and mortality. Unlike other chronic conditions, few data are available on the molecular mechanisms underlying muscle wasting in this clinical setting. Aims: To assess mechanisms of muscle atrophy in patients with cirrhosis. Methods: Nutritional [subjective global assessment (SGA) and anthropometry] and metabolic assessment was performed in 30 cirrhotic patients awaiting liver transplantation. Rectus abdominis biopsies were obtained intraoperatively in 22 cirrhotic patients and in 10 well-nourished subjects undergoing elective surgery for non-neoplastic disease, as a control group. Total RNA was extracted and mRNA for atrogenes (MuRF-1, Atrogin-1/MAFbx), myostatin (MSTN), GSK3β and IGF-1 was assayed. Results: A total of 50% of cirrhotic patients were malnourished based on SGA, while 53% were muscle-depleted according to mid-arm muscle area (MAMA<5th percentile). MuRF-1 RNA expression was significantly increased in malnourished cirrhotic patients (SGA-B/C) vs. well-nourished patients (SGA-A) (P = 0.01). The phosphorylation of GSK3β was up-regulated in cirrhotic patients with hepatocellular carcinoma (HCC) vs. patients without tumour (P < 0.05). Conclusions: Muscle loss is frequently found in end-stage liver disease patients. Molecular factors pertaining to signalling pathways known to be involved in the regulation of muscle mass are altered during cirrhosis and HCC. © 2013 John Wiley & Sons A/S

Effect of the specific proteasome inhibitor Bortezomib on cancer-related muscle wasting

Background: Muscle wasting, a prominent feature of cancer cachexia, is mainly caused by sustained protein hypercatabolism. The enhanced muscle protein degradation rates rely on the activity of different proteolytic systems, although the Adenosine triphosphate (ATP)-ubiquitin-proteasome-dependent pathway and autophagy have been shown to play a pivotal role. Bortezomib is a potent reversible and selective proteasome and NF-κB inhibitor approved for the clinical use, which has been shown to be effective in preventing muscle wasting in different catabolic conditions. The aim of the present study has been to investigate whether pharmacological inhibition of proteasome by bortezomib may prevent skeletal muscle wasting in experimental cancer cachexia. Methods: Cancer cachexia was induced in rats by intraperitoneal injection of Yoshida AH-130 ascites hepatoma cells and in mice by subcutaneous inoculation of C26 carcinoma cells. Animals were then further randomized to receive bortezomib. The AH-130 hosts were weighted and sacrificed under anaesthesia, on Days 3, 4, 5, and 7 after tumour inoculation, while C26-bearing mice were weighted and sacrificed under anaesthesia 12 days after tumour transplantation. NF-κB and proteasome activation, MuRF1 and atrogin-1 mRNA expression and beclin-1 protein levels were evaluated in the gastrocnemius of controls and AH-130 hosts. Results: Bortezomib administration in the AH-130 hosts, although able to reduce proteasome and NF-κB DNA-binding activity in the skeletal muscle on Day 7 after tumour transplantation, did not prevent body weight loss and muscle wasting. In addition, bortezomib exerted a transient toxicity, as evidenced by the reduced food intake and by the increase in NF-κB DNA-binding activity in the AH-130 hosts 3 days after tumour transplantation. Beclin-1 protein levels were increased by bortezomib treatment in Day 3 controls but were unchanged on both Days 3 and 7 in the AH-130 hosts, suggesting that an early compensatory induction of autophagy may exist in healthy but not in tumour-bearing animals. Regarding C26-bearing mice, bortezomib did not prevent as well body and muscle weight loss 12 days after tumour implantation. Conclusions: The results obtained suggest that proteasome inhibition by bortezomib is not able to prevent muscle wasting in experimental cancer cachexia. Further studies are needed to address the issue whether a different dosage of bortezomib alone or in combination with other drugs modulating different molecular pathways may effectively prevent muscle wasting during cancer cachexia. © 2015 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society of Sarcopenia, Cachexia and Wasting Disorder