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Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases.

ABSTRACT: Differential evolution of apoptosis, programmed necrosis, and autophagy, parthanatos is a form of cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1), which is caused by DNA damage. PARP1 hyper-activation stimulates apoptosis-inducing factor (AIF) nucleus translocation, and accelerates nicotinamide adenine dinucleotide (NAD⁺) and adenosine triphosphate (ATP) depletion, leading to DNA fragmentation. The mechanisms of parthanatos mainly include DNA damage, PARP1 hyper-activation, PAR accumulation, NAD⁺ and ATP depletion, and AIF nucleus translocation. Now, it is reported that parthanatos widely exists in different diseases (tumors, retinal diseases, neurological diseases, diabetes, renal diseases, cardiovascular diseases, ischemia-reperfusion injury...). Excessive or defective parthanatos contributes to pathological cell damage; therefore, parthanatos is critical in the therapy and prevention of many diseases. In this work, the hallmarks and molecular mechanisms of parthanatos and its related disorders are summarized. The questions raised by the recent findings are also presented. Further understanding of parthanatos will provide a new treatment option for associated conditions.

SUBMITTER: Huang P

PROVIDER: S-EPMC9266317 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases.

Huang Ping P Chen Guangwei G Jin Weifeng W Mao Kunjun K Wan Haitong H He Yu Y

International journal of molecular sciences 20220630 13

Differential evolution of apoptosis, programmed necrosis, and autophagy, parthanatos is a form of cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1), which is caused by DNA damage. PARP1 hyper-activation stimulates apoptosis-inducing factor (AIF) nucleus translocation, and accelerates nicotinamide adenine dinucleotide (NAD<sup>+</sup>) and adenosine triphosphate (ATP) depletion, leading to DNA fragmentation. The mechanisms of parthanatos mainly include DNA damage, PARP1 hyper-activatio ...[more]

PMID: 35806303

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Project description:Simple Summary Cachexia has been generally associated with cancer causing skeletal muscle atrophy, adipose tissue atrophy, weight loss, anorexia, asthenia, and anemia, which can significantly reduce the quality of life. Our aim was to evaluate the potential effects of bergamottin on cancer-cachexia-induced muscle and fat loss. We observed a decrease in the levels of the muscle atrophy factors MuRF-1 and Atrogin-1 and increases in C/EBPα and PPARγ expression levels by bergamottin under in vitro settings. The in vivo effect of bergamottin on the inhibition of weight loss in mice and its potential inhibitory effects on cancer-induced cachexia were confirmed through analysis using tissue samples from a pancreatic cancer mouse model. Abstract Purpose: The potential effects of bergamotiin (BGM) on the suppression of cancer cachexia was evaluated under in vitro and in vivo conditions to investigate its possible inhibitory effects on the muscle and fat loss. Method: The differentiated C2C12 and 3T3L1 cells were treated with BGM after the induction of cancer-cachexia with pancreatic cancer conditioned media (CM). The expression levels of the various molecules involved in the differentiation and loss of muscle and fat (MuRF-1, Atrogin-1, C/EBPα, and PPARγ) were analyzed by Western blot and oil red O staining. For in vivo experiment, MIA PaCa-2 cells were injected into the mice (n = 6), and then BGM (1 mg/kg) was intraperitoneally administered to analyze muscle and adipose tissue by Hematoxylin and Eosin staining and Western blot. Result: BGM displayed a significant effect on the inhibition of muscle and fat catabolism under both in vitro and in vivo conditions. The results of the in vivo experiment revealed a remarkable suppressive effect of BGM on the weight loss in mice. Conclusions: The potential effects of BGM on the inhibition of muscle and fat catabolism in vitro and in vivo were thus confirmed. Based on the results, the impact of BGM on cancer cachexia could be possibly analyzed in the future clinical studies.

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Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases.

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Molecular Mechanisms of Parthanatos and Its Role in Diverse Diseases.

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