Naslov
Changes in the proteome of extracellular vesicles shed by rat liver after subtoxic exposure to acetaminophen

Autori
Kovač Peić, Anamarija ; Šrajer Gajdošik, Martina ; Brilliant, Kate ; Callanan, Helen ; Hixson, Douglas C. ; Begić, Marija ; Josić, Djuro

Izvornik
Electrophoresis (0173-0835) 42 (2021); 1388-1398

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Acetaminophen subtoxic exposure / Extracellular vesicles / Liver / Perfusion / Proteome

Sažetak
To identify changes in extracellular vesicles (EVs) secreted by the liver following drug- induced liver injury (DILI), rats were treated with a subtoxic dose (500 mg/kg) of the analgesic drug, acetaminophen (APAP). EVs were collected by liver perfusion of sham and APAP- treated rats. Changes in EVs morphology were examined by transmission electron microscopic analysis of negatively stained vesicles. Results from morphometric analysis of EVs revealed striking differences in their size and distribution. Proteome composition of EVs collected by liver perfusion was determined by mass spectrometry using methods of sample preparation that enabled better detection of both highly hydrophobic proteins and proteins with complex post-translational modifications. The collection of EVs after liver perfusion is an approach that enables the isolation of EVs shed not only by isolated hepatocytes, but also by the entire complement of hepatic cells. EVs derived after DILI had a lower content of alpha-1-macroglobulin, ferritin, and members of cytochrome 450 family. Fibronectin, aminopeptidase N, metalloreductase STEAP4, integrin beta, and members of the annexin family were detected only in APAP-treated samples of EVs. These results show that the present approach can provide valuable insights into the response of the liver following drug- induced liver injury.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Temeljne medicinske znanosti, Biotehnologija u biomedicini (prirodno područje, biomedicina i zdravstvo, biotehničko područje)

POVEZANOST RADA