Mitochondrial function in sepsis

Jeger, Victor; Djafarzadeh, Siamak; Jakob, Stephan M.; Takala, Jukka

doi:10.1111/eci.12069

Cited by 73 publications

(66 citation statements)

References 74 publications

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“…Therefore discrepancy between present and past findings in skeletal muscle probably reflects compartmentalization of response to infection [37]. However, we cannot exclude that it simply indicates that skeletal muscle mitochondrial biochemistry is not, at least constantly, altered during sepsis [38].…”

Section: Discussioncontrasting

confidence: 57%

Mitochondrial Changes in Platelets Are Not Related to Those in Skeletal Muscle during Human Septic Shock

et al. 2014

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Platelets can serve as general markers of mitochondrial (dys)function during several human diseases. Whether this holds true even during sepsis is unknown. Using spectrophotometry, we measured mitochondrial respiratory chain biochemistry in platelets and triceps brachii muscle of thirty patients with septic shock (within 24 hours from admission to Intensive Care) and ten surgical controls (during surgery). Results were expressed relative to citrate synthase (CS) activity, a marker of mitochondrial density. Patients with septic shock had lower nicotinamide adenine dinucleotide dehydrogenase (NADH)/CS (p = 0.015), complex I/CS (p = 0.018), complex I and III/CS (p<0.001) and complex IV/CS (p = 0.012) activities in platelets but higher complex I/CS activity (p = 0.021) in triceps brachii muscle than controls. Overall, NADH/CS (r2 = 0.00; p = 0.683) complex I/CS (r2 = 0.05; p = 0.173), complex I and III/CS (r2 = 0.01; p = 0.485), succinate dehydrogenase (SDH)/CS (r2 = 0.00; p = 0.884), complex II and III/CS (r2 = 0.00; p = 0.927) and complex IV/CS (r2 = 0.00; p = 0.906) activities in platelets were not associated with those in triceps brachii muscle. In conclusion, several respiratory chain enzymes were variably inhibited in platelets, but not in triceps brachii muscle, of patients with septic shock. Sepsis-induced mitochondrial changes in platelets do not reflect those in other organs.

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Section: Discussioncontrasting

confidence: 57%

Mitochondrial Changes in Platelets Are Not Related to Those in Skeletal Muscle during Human Septic Shock

et al. 2014

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“…Several categories of proteins were affected by the proteolysis detected in our study: heat shock proteins related to mitochondrial function, which are known to be impaired in shock [23, 24];serine protease inhibitors (Inter alpha-trypsin inhibitors, serine protease inhibitor A3N and A3K, plasma protease C1 inhibitor, alpha macroglobulins, etc. ), indicating a possible response of the anti-proteases to the increased concentrations of circulating serine proteases in shock, and possibly suggesting that the increased protease activity produces extensive proteolysis because of a failure of the physiologic self-defense against proteases;…”

Section: Discussionmentioning

confidence: 93%

Peptidomic Analysis of Rat Plasma

Aletti

Maffioli

Negri

et al. 2016

Shock

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It has been previously shown that intestinal proteases translocate into the circulation during hemorrhagic shock and contribute to proteolysis in distal organs. However, consequences of this phenomenon have not previously been investigated using high-throughput approaches. Here, a shotgun label-free quantitative proteomic approach was utilized to compare the peptidome of plasma samples from healthy and hemorrhagic shock rats to verify the possible role of uncontrolled proteolytic activity in shock. Plasma was collected from rats after hemorrhagic shock (HS) consisting of two-hour hypovolemia followed by two-hour reperfusion, and from healthy control (CTRL) rats. A new two-step enrichment method was applied to selectively extract peptides and low molecular weight proteins from plasma, and directly analyze these samples by tandem mass spectrometry. 126 circulating peptides were identified in CTRL and 295 in HS animals. 96 peptides were present in both conditions; of these, 57 increased and 30 decreased in shock. In total, 256 peptides were increased or present only in HS confirming a general increase in proteolytic activity in shock. Analysis of the proteases that potentially generated the identified peptides suggests that the larger relative contribution of to the proteolytic activity in shock is due to chymotryptic-like proteases. These results provide quantitative confirmation that extensive, system-wide proteolysis is part of the complex pathologic phenomena occurring in hemorrhagic shock.

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“…In addition, a high variability of mitochondrial function among organs and tissues should not be ruled out. 26 For example, whereas in cardiac muscle of rodents a reduced enzymatic activity of certain complexes of respiratory chain has been described, a higher efficiency of respiration was observed in liver. 26 In our study, it is important to point out that sites of infection were different depending on the type of surgery carried out, as expected.…”

Section: Discussionmentioning

confidence: 99%

“…26 For example, whereas in cardiac muscle of rodents a reduced enzymatic activity of certain complexes of respiratory chain has been described, a higher efficiency of respiration was observed in liver. 26 In our study, it is important to point out that sites of infection were different depending on the type of surgery carried out, as expected. Therefore, differences in mitochondrial function among organs and tissues could lead to different ability to respond against an invading organism at the site of infection and thus, increase or decrease the susceptibility to sepsis after surgery.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA haplogroups are associated with severe sepsis and mortality in patients who underwent major surgery

Jiménez‐Sousa

Tamayo

Guzmán-Fulgencio

et al. 2015

Journal of Infection

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Mitochondrial function in sepsis

Abstract: Background The relevance of mitochondrial dysfunction as to pathogenesis of multiple organ dysfunction and failure in sepsis is controversial. This focused review evaluates the evidence for impaired mitochondrial function in sepsis.

Cited by 73 publications

References 74 publications

Mitochondrial Changes in Platelets Are Not Related to Those in Skeletal Muscle during Human Septic Shock

Mitochondrial Changes in Platelets Are Not Related to Those in Skeletal Muscle during Human Septic Shock

Peptidomic Analysis of Rat Plasma

Mitochondrial DNA haplogroups are associated with severe sepsis and mortality in patients who underwent major surgery

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