Sepsis-induced increase in muscle proteolysis is blocked by specific proteasome inhibitors

Hobler, Scott C.; Tiao, Greg; Fischer, Josef E.; Monaco, John J.; Hasselgren, Per-Olof

doi:10.1152/ajpregu.1998.274.1.r30

Cited by 57 publications

(60 citation statements)

References 30 publications

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“…Glycolysis is favored over oxidative phosphorylation despite adequate oxygen availability ("aerobic glycolysis", sometimes called the Warburg Effect) [206][207][208]. There is accelerated catabolism of skeletal muscle and perhaps smooth muscle as well [209]. In addition, micronutrient (e.g., vitamins, trace metals) effects are also impaired, reflecting either deficiency or altered activity [210,211].…”

Section: Basic/translational Science What Mechanisms Underlie Sepsis-mentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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Objective: To identify research priorities in the management, epidemiology, outcome and underlying causes of sepsis and septic shock.Design: A consensus committee of 16 international experts representing the European Society of Intensive Care Medicine and Society of Critical Care Medicine was convened at the annual meetings of both societies. Subgroups had teleconference and electronic-based discussion. The entire committee iteratively developed the entire document and recommendations.Methods: Each committee member independently gave their top five priorities for sepsis research. A total of 88 suggestions (ESM 1 -supplemental table 1) were grouped into categories by the committee co-chairs, leading to the formation of seven subgroups: infection, fluids and vasoactive agents, adjunctive therapy, administration/epidemiology, scoring/identification, post-intensive care unit, and basic/translational science. Each subgroup had teleconferences to go over each priority followed by formal voting within each subgroup. The entire committee also voted on top priorities across all subgroups except for basic/translational science. Results:The Surviving Sepsis Research Committee provides 26 priorities for sepsis and septic shock. Of these, the top six clinical priorities were identified and include the following questions: (1) can targeted/personalized/precision medicine approaches determine which therapies will work for which patients at which times?; (2) what are ideal endpoints for volume resuscitation and how should volume resuscitation be titrated?; (3) should rapid diagnostic tests be implemented in clinical practice?; (4) should empiric antibiotic combination therapy be used in sepsis or septic shock?; (5) what are the predictors of sepsis long-term morbidity and mortality?; and (6) what information identifies organ dysfunction?Conclusions: While the Surviving Sepsis Campaign guidelines give multiple recommendations on the treatment of sepsis, significant knowledge gaps remain, both in bedside issues directly applicable to clinicians, as well as understanding the fundamental mechanisms underlying the development and progression of sepsis. The priorities identified represent a roadmap for research in sepsis and septic shock.

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Section: Basic/translational Science What Mechanisms Underlie Sepsis-mentioning

confidence: 99%

Surviving sepsis campaign: research priorities for sepsis and septic shock

et al. 2018

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“…The process was shown to affect total and myofibrillar protein levels and to be associated with elevated ubiquitin mRNA. Subsequent work has established that the response is greater in fastthan in slow-twitch muscle (705) and that sepsis-stimulated proteolysis can be blocked using proteasome inhibitors, both in isolated muscle preparations (315) and intact animals (200) (FIGURE 11E).…”

Section: A the Ubiquitin-proteasome Pathway In Critical Illnessmentioning

confidence: 99%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

300

329

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Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca 2ϩ dysregulation is present through altered Ca 2ϩ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

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“…Further, this critical adaptive process of skeletal muscle might facilitate an attenuation in the indirect markers of EIMD following protein consumption (Saunders, 2007). Willoughby et al, (2003) reported an up-regulation of the ubiquitin-proteolytic pathway 48 h following an eccentric exercise bout; indicative of conditions that result in a reduced myofibrillar protein content (Hobler et al, 1998). Hence, efforts to alter protein metabolism and support myofibrillar protein synthesis as soon as possible following EIMD might facilitate recovery.…”

Section: Introductionmentioning

confidence: 99%

The efficacy of protein supplementation during recovery from muscle-damaging concurrent exercise

Eddens

Browne

Stevenson

et al. 2017

Appl. Physiol. Nutr. Metab.

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Northumbria University has developed Northumbria Research Link (NRL) to enable users to access the University's research output. Copyright © and moral rights for items on NRL are retained by the individual author(s) and/or other copyright owners. Single copies of full items can be reproduced, displayed or performed, and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided the authors, title and full bibliographic details are given, as well as a hyperlink and/or URL to the original metadata page. The content must not be changed in any way. Full items must not be sold commercially in any format or medium without formal permission of the copyright holder. The full policy is available online: http://nrl.northumbria.ac.uk/policies.html This document may differ from the final, published version of the research and has been made available online in accordance with publisher policies. To read and/or cite from the published version of the research, please visit the publisher's website (a subscription may be required.) AbstractThis study investigated the effect of protein supplementation on recovery following muscle-damaging exercise, which was induced with a concurrent exercise design. Twenty-four well-trained male cyclists were randomised to three independent groups receiving 20 g protein hydrolysate, iso-caloric carbohydrate or low-calorific placebo supplementation, per serve. Supplement serves were provided twice daily, from the onset of the muscle-damaging exercise, for a total of four days and in addition to a controlled diet (6 g·kg

show abstract

Sepsis-induced increase in muscle proteolysis is blocked by specific proteasome inhibitors

Cited by 57 publications

References 30 publications

Surviving sepsis campaign: research priorities for sepsis and septic shock

Surviving sepsis campaign: research priorities for sepsis and septic shock

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

The efficacy of protein supplementation during recovery from muscle-damaging concurrent exercise

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