c-Jun N-Terminal Kinase Plays a Major Role in Murine Acetaminophen Hepatotoxicity

Gunawan, Basuki; Liu, Zhang–Xu; Han, Derick; Hanawa, Naoko; Gaarde, William A.; Kaplowitz, Neil

doi:10.1053/j.gastro.2006.03.045

Cited by 420 publications

(463 citation statements)

References 47 publications

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“…Similar observation was made when a chemical JNK inhibitor was used. 37 This was not the case in a previously reported study in that JNK1 or JNK2-deficient mice were protected. 15 The reason for this discrepancy is not clear.…”

Section: Differential Role Of Jnk In Cona Versus Cona/ Galn-induced Lmentioning

confidence: 74%

“…For example, JNK is critical for acetaminophen-induced liver injury, which is characterized by caspase-independent oncotic necrosis. 37 This effect of JNK is specific to this type of injury and was not observed in injury caused by CCl 4 or ConA. 37 In summary, ConA stimulation of liver injury evokes different cell death modes depending on the presence of the sensitizing agent, GalN.…”

Section: Differential Role Of Jnk In Cona Versus Cona/ Galn-induced Lmentioning

confidence: 98%

“…37 This effect of JNK is specific to this type of injury and was not observed in injury caused by CCl 4 or ConA. 37 In summary, ConA stimulation of liver injury evokes different cell death modes depending on the presence of the sensitizing agent, GalN. Whereas ConA alone mainly induce a caspase-independent necrotic death and mild reversible liver injury, ConA/GalN also activates a potent caspase-dependent apoptotic response, in which JNK participates to promote mitochondria activation, leading to irreversible liver injury and mortality.…”

Section: Differential Role Of Jnk In Cona Versus Cona/ Galn-induced Lmentioning

confidence: 99%

See 2 more Smart Citations

Differential Roles of JNK in ConA/GalN and ConA-Induced Liver Injury in Mice

Chen

Ding

et al. 2008

The American Journal of Pathology

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Section: Differential Role Of Jnk In Cona Versus Cona/ Galn-induced Lmentioning

confidence: 74%

Section: Differential Role Of Jnk In Cona Versus Cona/ Galn-induced Lmentioning

confidence: 98%

Section: Differential Role Of Jnk In Cona Versus Cona/ Galn-induced Lmentioning

confidence: 99%

See 1 more Smart Citation

Differential Roles of JNK in ConA/GalN and ConA-Induced Liver Injury in Mice

Chen

Ding

et al. 2008

The American Journal of Pathology

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“…JNK activation, particularly in the mitochondria, has been shown to exacerbate APAP-induced liver injury (24,25,27,47).…”

Section: Jnk Activation Was Differentially Regulated In Parkin Ko Andmentioning

confidence: 99%

Chronic Deletion and Acute Knockdown of Parkin Have Differential Responses to Acetaminophen-induced Mitophagy and Liver Injury in Mice

Williams

Haynes

et al. 2015

Journal of Biological Chemistry

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Background: Parkin is required for mitophagy in cultured cells, but its role in liver injury is not known. Results: APAP-induced mitophagy was impaired in acute Parkin knockdown mouse livers but not whole body Parkin knock-out mice. Conclusion: Chronic, but not acute, loss of Parkin protects against APAP-induced liver injury by multiple mechanisms independent of mitophagy. Significance: This study revealed a novel role of Parkin in APAP-induced liver injury.

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“…Activation of hepatic JNK is recognized as a key event in the progression and exacerbation of acetaminophen toxicity, and inhibition of p-JNK has been shown to protect mice against acetaminophen-induced hepatotoxicity (28,29). In the present study, Schisandra chinensis was found to inhibit p-JNK expression levels compared with those in the acetaminophen-treated hepatocytes…”

Section: Discussionmentioning

confidence: 52%

Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity

Wang

Bai

Wang

et al. 2014

Molecular Medicine Reports

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Abstract. Schisandra chinensis is a well-known traditional medicinal herb. Acetaminophen is a commonly used over-the-counter analgesic and overdose of acetaminophen was the most frequent cause of acute liver failure. However, no studies have demonstrated the role of Schisandra chinensis in acetaminophen-induced acute liver failure to the best of our knowledge. In this study, an acute liver injury model was established in mice using acetaminophen. The protective role of Schisandra chinensis was detected by histopathological analysis, and measurement of the serum transaminase levels and hepatic Cyp activity levels in the mouse model. Subsequently, hepatocytes were isolated from the livers of the mouse model. The cell cycle, apoptosis, mitochondrial membrane potential and reactive oxygen species were determined using flow cytometry. Cell proliferation and 26S proteasome activity were determined using spectrophotometry. Schisandra chinensis was found to resist acetaminophen-induced hepatotoxicity by protecting mitochondria and lysosomes and inhibiting the phosphor-c-Jun N-terminal kinase signaling pathway. These findings provide a novel application of Schisandra chinensis against acetaminophen-induced acute liver failure.

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c-Jun N-Terminal Kinase Plays a Major Role in Murine Acetaminophen Hepatotoxicity

Cited by 420 publications

References 47 publications

Differential Roles of JNK in ConA/GalN and ConA-Induced Liver Injury in Mice

Differential Roles of JNK in ConA/GalN and ConA-Induced Liver Injury in Mice

Chronic Deletion and Acute Knockdown of Parkin Have Differential Responses to Acetaminophen-induced Mitophagy and Liver Injury in Mice

Inhibitory effects of Schisandra chinensis on acetaminophen-induced hepatotoxicity

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