Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis

Klaude, Maria; Fredriksson, Katarina; Tjäder, Inga; Hammarqvist, Folke; Ahlman, B.; Rooyackers, Olav; Wernerman, Jan

doi:10.1042/cs20060265

Cited by 104 publications

(78 citation statements)

References 34 publications

(39 reference statements)

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“…More recently, increased activity of the proteasome and direct evidence for increased muscle proteolysis have been shown in both respiratory (30% increase compared with controls) and limb (45-55% increase compared with controls) muscle of septic patients in the ICU [35].…”

Section: Upregulation Of Muscle Protein Breakdown In Icuawmentioning

confidence: 99%

Molecular mechanisms of intensive care unit-acquired weakness

Bloch¹,

Polkey²,

Griffiths³

et al. 2011

Eur Respir J

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Intensive care unit-acquired weakness (ICUAW) is an increasingly recognised and important clinical consequence of critical illness. It is associated with significant morbidity and mortality. The aetiology of this disease is not well understood. The purpose of this article is to review our understanding of the molecular pathogenesis of ICUAW in the context of current knowledge of clinical risk factors and aetiology.Key features of the disease are loss of muscle mass resulting from a shift in the dynamic balance of muscle protein synthesis and breakdown and a reduction in force-generating capacity. These alternations are secondary to neuropathy, disruption of the myofilament structure and function, a disrupted sarcoplasmic reticulum, electrical inexcitability and bioenergenetic failure.As knowledge and understanding of ICUAW grows, potential therapeutic targets will be identified, hopefully leading to multiple strategies for prevention and treatment of this important condition.

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Section: Upregulation Of Muscle Protein Breakdown In Icuawmentioning

confidence: 99%

Molecular mechanisms of intensive care unit-acquired weakness

Bloch¹,

Polkey²,

Griffiths³

et al. 2011

Eur Respir J

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“…der kalziumabhängi-gen Calpaine kommt [55,69,121]. Dabei ist es vermutlich das Ziel dieser katabolen Vorgänge, dem Organismus vermehrt freie Aminosäuren zur Verfügung zu stellen, um den gesteigerten Bedarf zu decken.…”

Section: > Die Cim Tritt Häufiger Und Früher Auf Als Die Cipunclassified

Erworbene Muskelschwäche beim kritisch Kranken

et al. 2011

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Intensive care unit-acquired weakness (ICUAW) is a severe complication in critically ill patients which has been increasingly recognized over the last two decades. By definition ICUAW is caused by distinct neuromuscular disorders, namely critical illness polyneuropathy (CIP) and critical illness myopathy (CIM). Both CIP and CIM can affect limb and respiratory muscles and thus complicate weaning from a ventilator, increase the length of stay in the intensive care unit and delay mobilization and physical rehabilitation. It is controversially discussed whether CIP and CIM are distinct entities or whether they just represent different organ manifestations with common pathomechanisms. These basic pathomechanisms, however, are complex and still not completely understood but metabolic, inflammatory and bioenergetic alterations seem to play a crucial role. In this respect several risk factors have recently been revealed: in addition to the administration of glucocorticoids and non-depolarizing muscle relaxants, sepsis and multi-organ failure per se as well as elevated levels of blood glucose and muscular immobilization have been shown to have a profound impact on the occurrence of CIP and CIM. For the diagnosis, careful physical and neurological examinations, electrophysiological testing and in rare cases nerve and muscle biopsies are recommended. Nevertheless, it appears to be difficult to clearly distinguish between CIM and CIP in a clinical setting. At present no specific therapy for these neuromuscular disorders has been established but recent data suggest that in addition to avoidance of risk factors early active mobilization of critically ill patients may be beneficial.

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“…Experimental and human studies have clearly demonstrated that proteasome activities increase in wasting condition such as cancer (Bossola et al 2003), burns (Chai et al 2002), sepsis (Klaude et al 2007), chronic obstructive pulmonary disease (Ottenheijm et al 2006), chronic renal failure (Raj et al 2003), congestive heart failure (Filippatos et al 2005), as well as in disuse or denervation atrophy (Kandarian and Stevenson 2002).…”

Section: Introductionmentioning

confidence: 98%

Proteasome activities in the rectus abdominis muscle of young and older individuals

et al. 2008

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Sarcopenia is one of the most striking effects of age, the causes and the pathogenic mechanisms being largely unknown. Unfortunately, there is limited information on the effect of aging on muscle protein breakdown in basal conditions. The present study aimed at investigating if skeletal muscle ubiquitn mRNA levels and proteasome activities vary with age in healthy individuals. Ub mRNA levels were measured by northern blot analysis whereas proteasome activities were determined by evaluating the cleavage of specific fluorogenic substrates in the rectus abdominis muscle of 14 healthy male individuals. Patients were divided in three groups according to the age: (1) 20-30 years (N = 3); (2) 31-64 years (N = 5); (3) > or = 65 years (N = 6). Quantitation of the ubiquitin mRNA levels (expressed in arbitrary units) (mean (SD) showed no differences among the three groups of age (20-30 years: 1352 +/- 441; 31-64 years: 1324 +/- 439; > or = 65 years: 884 +/- 400; P = 0.33). The correlation between age and muscle ubiquitin mRNA levels was not statistically significant (r = -0.4, P = 0.26). The three proteasome activities, chymotrypsin-like (CTL), trypsin-like (TL) and peptidyl-gutamyl-peptidase (PGP), expressed as nkatal x 10(-3)/mg protein, were similar in the three groups of patients stratified according to the age. There was no correlation between age with either CTL (r = 0.22, P = 0.4), PGP (r = 0.002, P = 0.9), and TL (r = 0.28, P = 0.33) activities. In conclusion, the present study shows that the skeletal muscle proteasome activities do not differ with age in healthy male individuals.

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Proteasome proteolytic activity in skeletal muscle is increased in patients with sepsis

Cited by 104 publications

References 34 publications

Molecular mechanisms of intensive care unit-acquired weakness

Molecular mechanisms of intensive care unit-acquired weakness

Erworbene Muskelschwäche beim kritisch Kranken

Proteasome activities in the rectus abdominis muscle of young and older individuals

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