Mechanisms of Acetaminophen Hepatotoxicity: Cell Death Signaling Mechanisms in Hepatocytes

AbstractMost currently recommended therapies for metabolic dysfunction-associated fatty liver disease (MAFLD) involve diet control and exercise therapy. We searched PubMed and compiled the most recent research into possible forms of programmed cell death in MAFLD, including apoptosis, necroptosis, autophagy, pyroptosis and ferroptosis. Here, we summarize the state of knowledge on the signaling mechanisms for each type and, based on their characteristics, discuss how they might be relevant in MAFLD-related pathological mechanisms. Although significant challenges exist in the translation of fundamental science into clinical therapy, this review should provide a theoretical basis for innovative MAFLD clinical treatment plans that target programmed cell death.

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RETRACTED: Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicity

Journal of Hepatology ◽

10.1016/j.jhep.2011.12.019 ◽

2012 ◽

Vol 56 (5) ◽

pp. 1070-1079 ◽

Cited By ~ 239

Author(s):

Daniel J. Antoine ◽

Rosalind E. Jenkins ◽

James W. Dear ◽

Dominic P. Williams ◽

Mitchell R. McGill ◽

...

Keyword(s):

Cell Death ◽

Molecular Forms ◽

Keratin 18 ◽

Acetaminophen Hepatotoxicity

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Cell Death Related Proteins Beyond Apoptosis in the CNS

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.825747 ◽

2022 ◽

Vol 9 ◽

Author(s):

Bazhena Bahatyrevich-Kharitonik ◽

Rafael Medina-Guzman ◽

Alicia Flores-Cortes ◽

Marta García-Cruzado ◽

Edel Kavanagh ◽

...

Keyword(s):

Cell Death ◽

Protein Function ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Original Function ◽

New Concepts ◽

Cytoskeleton Reorganization ◽

Caspase Substrates ◽

Cell Death Signaling ◽

Related Proteins

Cell death related (CDR) proteins are a diverse group of proteins whose original function was ascribed to apoptotic cell death signaling. Recently, descriptions of non-apoptotic functions for CDR proteins have increased. In this minireview, we comment on recent studies of CDR proteins outside the field of apoptosis in the CNS, encompassing areas such as the inflammasome and non-apoptotic cell death, cytoskeleton reorganization, synaptic plasticity, mitophagy, neurodegeneration and calcium signaling among others. Furthermore, we discuss the evolution of proteomic techniques used to predict caspase substrates that could potentially explain their non-apoptotic roles. Finally, we address new concepts in the field of non-apoptotic functions of CDR proteins that require further research such the effect of sexual dimorphism on non-apoptotic CDR protein function and the emergence of zymogen-specific caspase functions.

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Differentiating life and death: An inflammatory affair

10.7287/peerj.preprints.27080v1 ◽

2018 ◽

Author(s):

Dustin Lane

Keyword(s):

Cell Cycle ◽

Dna Damage ◽

Cell Death ◽

Cell Differentiation ◽

Programmed Cell Death ◽

Signaling Networks ◽

Inhibitors Of Apoptosis ◽

Life And Death ◽

Cell Death Signaling ◽

Cycle Dependent

Programmed cell death signaling networks are frequently activated to coordinate the process of cell differentiation, and a variety of apoptotic events can mediate the process. This can include the ligation of death receptors, the activation of downstream caspases, and the induction of chromatin fragmentation, and all of these events can occur without downstream induction of death. Importantly, regulators of programmed cell death also have established roles in mediating differentiation. This review will provide an overview of apoptosis and its regulation by Inhibitors of Apoptosis (IAPs) and Bcl-2 family members. It will then outline the cross-talk between NF-ĸB and apoptotic signaling in the regulation of apoptosis before discussing the function of these regulators in the control of cell differentiation. It will end on a discussion of how a DNA damage-directed, cell cycle-dependent differentiation program may be controlled across multiple passages through cell cycle, and will assert that the failure to properly differentiate is the underlying cause of cancer.

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