Dose response of endotoxin on hepatocyte and muscle mitochondrial respiration in vitro.

Jeger, Victor; Brandt, Sebastian; Porta, Francesca; Jakob, Stephan; Takala, Jukka; Djafarzadeh, Siamak (2015). Dose response of endotoxin on hepatocyte and muscle mitochondrial respiration in vitro. BioMed research international, 2015, p. 353074. Hindawi Publishing Corporation 10.1155/2015/353074

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INTRODUCTION Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria. METHODS Human hepatocellular carcinoma cells (HepG2) were exposed to placebo or LPS (0.1, 1, and 10 μg/mL) for 4, 8, 16, and 24 hours and primary human hepatocytes to 1 μg/mL LPS or placebo (4, 8, and 16 hours). Mitochondria from porcine skeletal muscle samples were exposed to increasing doses of LPS (0.1-100 μg/mg) for 2 and 4 hours. Respiration rates of intact and permeabilized cells and isolated mitochondria were measured by high-resolution respirometry. RESULTS In HepG2 cells, LPS reduced mitochondrial membrane potential and cellular ATP content but did not modify basal respiration. Stimulated complex II respiration was reduced time-dependently using 1 μg/mL LPS. In primary human hepatocytes, stimulated mitochondrial complex II respiration was reduced time-dependently using 1 μg/mL LPS. In isolated porcine skeletal muscle mitochondria, stimulated respiration decreased at high doses (50 and 100 μg/mL LPS). CONCLUSION LPS reduced cellular ATP content of HepG2 cells, most likely as a result of the induced decrease in membrane potential. LPS decreased cellular and isolated mitochondrial respiration in a time-dependent, dose-dependent and complex-dependent manner.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Pavillon 52 > Forschungsgruppe Intensivmedizin
04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic of Intensive Care

UniBE Contributor:

Jakob, Stephan; Takala, Jukka and Djafarzadeh, Siamak

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2314-6133

Publisher:

Hindawi Publishing Corporation

Language:

English

Submitter:

Alessandra Angelini

Date Deposited:

13 Jan 2016 13:54

Last Modified:

06 Jul 2016 20:55

Publisher DOI:

10.1155/2015/353074

PubMed ID:

25649304

BORIS DOI:

10.7892/boris.74865

URI:

https://boris.unibe.ch/id/eprint/74865

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