Cytosolic p53 Inhibits Parkin-Mediated Mitophagy and Promotes Acute Liver Injury Induced by Heat Stroke

Huang, Wei; Xie, Weidang; Zhong, Hanhui; Cai, Shumin; Huang, Qiaobing; Liu, Youtan; Zeng, Zhenhua; Liu, Yanan

doi:10.3389/fimmu.2022.859231

Cited by 13 publications

(8 citation statements)

References 55 publications

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“…Through software prediction and experiments, we revealed that Ku70 could interact with Parkin in vivo and in vitro. Parkin, as E3 ubiquitin ligase, is expressed in various tissues and organs, being widely involved in disease progression [50][51][52]. Parkin mediated K63 ubiquitination of RIPK1 to activate nuclear factor-kappa B and mitogen-activated protein kinase [53].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitination of Ku70 by Parkin promotes apoptosis of lens epithelial cells

Zhang

et al. 2023

The FEBS Journal

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Oxidative damage‐triggered apoptosis in lens epithelial cells is considered as a main risk factor in the pathogenesis of age‐related cataracts. Ku70 is a key factor in the DNA repair process of double‐strand breaks. In the present study, we aimed to investigate the role of Ku70 and its related E3 ubiquitin ligase in lens epithelial cell apoptosis. The levels of Ku70 in the anterior lens capsules of human cataracts and Emory mice were lower compared to controls. H2O2 treatment resulted in decreased expression of Ku70 through accelerating Ku70 ubiquitination. Parkin, an E3 ubiquitin ligase, could interact with Ku70 and promote the ubiquitination and degradation of this protein. In addition, ubiquitinated Ku70 was regulated by ubiquitin‐proteasome, autophagy‐lysosome and mitophagy pathways. Ectopic expression of Ku70 protected SRA01/04 cells from H2O2‐induced apoptosis, whereas silencing Ku70 exhibited the opposite trend. Co‐transfected with Parkin non‐ubiquitinatable Ku70 mutant could maintain its anti‐apoptosis ability, whereas wild‐type Ku70 failed. Moreover, Ku70 might facilitate mitochondrial fusion by increasing the expression of Mitofusin 1/2. The present study revealed that Parkin‐mediated Ku70 ubiquitination facilitated H2O2‐induced lens epithelial cell apoptosis through alleviating mitochondrial fusion, which could provide potential targets for age‐related cataract treatment.

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Section: Discussionmentioning

confidence: 99%

Ubiquitination of Ku70 by Parkin promotes apoptosis of lens epithelial cells

Zhang

et al. 2023

The FEBS Journal

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“…The underlying physiological link between heatstroke and procalcitonin could be mediated by the exaggerated systemic in ammatory response that characterizes heatstroke [40]. Liver injury is a common complication of CHS and a signi cant cause of mortality [43]. When heat stroke occurs, the blood ow of the liver decreases, and at the same time, extensive microthrombosis occurs in the liver due to concurrent DIC, causing liver ischemia and hypoxia and eventually leading to liver damage [44].…”

Section: Discussionmentioning

confidence: 99%

Development and validation of a prognostic model of survival for classic heatstroke patients: A multicenter study

Wang

et al. 2023

Preprint

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Background Classic heatstroke (CHS) is a life-threatening illness characterized by extreme hyperthermia, dysfunction of the central nervous system and multiorgan failure. Accurate predictive models are useful in the treatment decision-making process and risk stratification.This study was to develop and externally validate a prediction model of survival for hospitalized patients with CHS. Methods In this retrospective study, we enrolled patients with CHS who were hospitalized from June 2022 to September 2022 at 3 hospitals in Southwest Sichuan (training cohort) and 1 hospital in Central Sichuan (external validation cohort). Prognostic factors were identified utilizing least absolute shrinkage and selection operator (LASSO) regression analysis and multivariate Cox regression analysis in the training cohort. A predictive model was developed based on identified prognostic factors, and a nomogram was built for visualization. The areas under the receiver operator characteristic (ROC) curves (AUCs) and the calibration curve were utilized to assess the prognostic performance of the model in both the training and external validation cohorts. The Kaplan‒Meier method was used to calculate survival rates. Result A total of 189 patients (median age, 75 [68–81] years) were included. Social isolation, self-care ability, comorbidities, body temperature, heart rate, Glasgow Coma Scale (GCS), procalcitonin (PCT), aspartate aminotransferase (AST) and diarrhea were found to have a significant or near-significant association with worse prognosis among hospitalized CHS patients. The AUCs of the model in the training and validation cohorts were 0.994 (95% [CI], 0.975–0.999) and 0.815 (95% [CI], 0.596–0.956), respectively. The model's prediction and actual observation demonstrated strong concordance on the calibration curve regarding 7-day survival probability. According to K‒M survival plots, there were significant differences in survival between the low-risk and high-risk groups in the training cohort and borderline significant differences in the external validation cohort. Conclusion We designed and externally validated a prognostic prediction nomogram for CHS. This model has promising predictive performance and could be applied in clinical practice for managing patients with CHS.

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“…In addition, p53 can dually regulate ferroptosis via diverse pathways [ 139 ]. Most interesting, it has been suggested that p53 will transfer to the mitochondria to regulate mitochondrial membrane potential and trigger cellular apoptosis under oxidative stress [ 140 , 141 ], and several proteins proven to interact with p53 directly or indirectly also locate in the mitochondria under the state of oxidative stress, such as MDM2 [ 142 ], FOXO3a [ 143 , 144 ], ATM, c-Abl [ 145 ], Parkin [ 146 ], and TERT [ 144 ] ( Figure 4 ).…”

Section: Oxidative Stress and The Relationship Between Death And Tumorsmentioning

confidence: 99%

The Role of Oxidative Stress in Tumorigenesis and Progression

Li,

Deng,

Lei

et al. 2024

Cells

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Oxidative stress refers to the imbalance between the production of reactive oxygen species (ROS) and the endogenous antioxidant defense system. Its involvement in cell senescence, apoptosis, and series diseases has been demonstrated. Advances in carcinogenic research have revealed oxidative stress as a pivotal pathophysiological pathway in tumorigenesis and to be involved in lung cancer, glioma, hepatocellular carcinoma, leukemia, and so on. This review combs the effects of oxidative stress on tumorigenesis on each phase and cell fate determination, and three features are discussed. Oxidative stress takes part in the processes ranging from tumorigenesis to tumor death via series pathways and processes like mitochondrial stress, endoplasmic reticulum stress, and ferroptosis. It can affect cell fate by engaging in the complex relationships between senescence, death, and cancer. The influence of oxidative stress on tumorigenesis and progression is a multi-stage interlaced process that includes two aspects of promotion and inhibition, with mitochondria as the core of regulation. A deeper and more comprehensive understanding of the effects of oxidative stress on tumorigenesis is conducive to exploring more tumor therapies.

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Cytosolic p53 Inhibits Parkin-Mediated Mitophagy and Promotes Acute Liver Injury Induced by Heat Stroke

Cited by 13 publications

References 55 publications

Ubiquitination of Ku70 by Parkin promotes apoptosis of lens epithelial cells

Ubiquitination of Ku70 by Parkin promotes apoptosis of lens epithelial cells

Development and validation of a prognostic model of survival for classic heatstroke patients: A multicenter study

The Role of Oxidative Stress in Tumorigenesis and Progression

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