Circulating 20S Proteasome Is Independently Associated with Abdominal Muscle Mass in Hemodialysis Patients

Abstract

Protein-energy wasting is highly prevalent in hemodialysis patients, and it contributes to patient morbidity and mortality. The ubiquitin-proteasome system is the major pathway for intracellular protein degradation and it is involved in the regulation of basic cellular processes. However, the role of this system in the determination of nutritional status is largely unknown. To examine a relationship between protein-energy wasting and the ubiquitin-proteasome system, a cross-sectional study of 76 hemodialysis patients was performed. Plasma concentrations of 20S proteasome were studied to evaluate its association with muscle and fat mass, which were investigated by abdominal muscle and fat areas measured using computed tomography and by creatinine production estimated using the creatinine kinetic model. Plasma 20S proteasome concentrations significantly and negatively correlated with abdominal muscle areas and creatinine production (rho = -0.263, P < 0.05 and rho = -0.241, P < 0.05, respectively), but not abdominal subcutaneous and visceral fat areas. Multiple regression analyses showed that 20S proteasome was a significant independent predictor of abdominal muscle area (P < 0.05). In conclusion, plasma 20S proteasome concentrations were independently associated with abdominal muscle mass in hemodialysis patients. Our findings indicate a relationship between circulating 20S proteasomes and muscle metabolism in these patients.Trial RegistrationUMIN Clinical Trials Registry UMIN000012341

Neuroinflammatory targets and treatments for epilepsy validated in experimental models

“…How the immunoproteasome could have a pro‐ictogenic effect is unknown. It could have either a specific role in the regulation of synaptic density or could act as enhancer of inflammatory milieu, as demonstrated for other neurological diseases . Of note, the immunoproteasome could regulate (neuro)inflammation not only as intracellular protease but also in the extracellular space.…”

“…There, it could regulate pro‐inflammatory functions of cytokines, as recently demonstrated for osteopontin in the multiple sclerosis context . Therefore, the immunoproteasome might be considered as a therapeutic target for pharmacoresistant epilepsies as it is already under investigation for cancers, Alzheimer’s disease, and other diseases …”

“…It could have either a specific role in the regulation of synaptic density or could act as enhancer of inflammatory milieu, as demonstrated for other neurological diseases. 47,51 Of note, the immunoproteasome could regulate (neuro)inflammation not only as intracellular protease but also in the extracellular space. There, it could regulate pro-inflammatory functions of cytokines, as recently demonstrated for osteopontin in the multiple sclerosis context.…”

“…52 Therefore, the immunoproteasome might be considered as a therapeutic target for pharmacoresistant epilepsies as it is already under investigation for cancers, Alzheimer's disease, and other diseases. 47…”

The Impact of Serum Zinc Levels on Abdominal Fat Mass in Hemodialysis Patients

“…The abdominal muscle area (AMA), abdominal subcutaneous fat area (ASFA), and abdominal visceral fat area (AVFA) were automatically measured using SYNAPSE VINCENT software (version 3.0, Fujifilm Medical, Tokyo, Japan), which enables the tissue segmentation using Hounsfield unit thresholds [15]. To avoid the potentially confounding influence of body size, we also adjusted AMA, ASFA, and AVFA by dividing by the height of each patient (AMA/height, ASFA/height, and AVFA/height, respectively) [16].…”