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Article

Loss of BOK Has a Minor Impact on Acetaminophen Overdose-Induced Liver Damage in Mice

1
Institute of Pharmacology, University of Bern, Inselspital, INO-F, 3010 Bern, Switzerland
2
Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Ave, Toronto, ON M4N 3M5, Canada
3
COMPATH, Institute of Animal Pathology, University of Bern, Laenggassstrasse 122, CH-3012 Bern, Switzerland
*
Author to whom correspondence should be addressed.
Academic Editor: Alain Couvineau
Int. J. Mol. Sci. 2021, 22(6), 3281; https://doi.org/10.3390/ijms22063281
Received: 13 February 2021 / Revised: 14 March 2021 / Accepted: 20 March 2021 / Published: 23 March 2021
(This article belongs to the Section Molecular Pharmacology)
Acetaminophen (APAP) is one of the most commonly used analgesic and anti-pyretic drugs, and APAP intoxication is one of the main reasons for liver transplantation following liver failure in the Western world. While APAP poisoning ultimately leads to liver necrosis, various programmed cell death modalities have been implicated, including ER stress-triggered apoptosis. The BCL-2 family member BOK (BCL-2-related ovarian killer) has been described to modulate the unfolded protein response and to promote chemical-induced liver injury. We therefore investigated the impact of the loss of BOK following APAP overdosing in mice. Surprisingly, we observed sex-dependent differences in the activation of the unfolded protein response (UPR) in both wildtype (WT) and Bok-/- mice, with increased activation of JNK in females compared with males. Loss of BOK led to a decrease in JNK activation and a reduced percentage of centrilobular necrosis in both sexes after APAP treatment; however, this protection was more pronounced in Bok-/- females. Nevertheless, serum ALT and AST levels of Bok-/- and WT mice were comparable, indicating that there was no major difference in the overall outcome of liver injury. We conclude that after APAP overdosing, loss of BOK affects initiating signaling steps linked to ER stress, but has a more minor impact on the outcome of liver necrosis. Furthermore, we observed sex-dependent differences that might be worthwhile to investigate. View Full-Text
Keywords: BOK; BCL-2 family; acetaminophen; ER stress; UPR; apoptosis; necrosis BOK; BCL-2 family; acetaminophen; ER stress; UPR; apoptosis; necrosis
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MDPI and ACS Style

Naim, S.; Fernandez-Marrero, Y.; de Brot, S.; Bachmann, D.; Kaufmann, T. Loss of BOK Has a Minor Impact on Acetaminophen Overdose-Induced Liver Damage in Mice. Int. J. Mol. Sci. 2021, 22, 3281. https://doi.org/10.3390/ijms22063281

AMA Style

Naim S, Fernandez-Marrero Y, de Brot S, Bachmann D, Kaufmann T. Loss of BOK Has a Minor Impact on Acetaminophen Overdose-Induced Liver Damage in Mice. International Journal of Molecular Sciences. 2021; 22(6):3281. https://doi.org/10.3390/ijms22063281

Chicago/Turabian Style

Naim, Samara, Yuniel Fernandez-Marrero, Simone de Brot, Daniel Bachmann, and Thomas Kaufmann. 2021. "Loss of BOK Has a Minor Impact on Acetaminophen Overdose-Induced Liver Damage in Mice" International Journal of Molecular Sciences 22, no. 6: 3281. https://doi.org/10.3390/ijms22063281

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