Arsenic Exposure-Induced Acute Kidney Injury by Regulating SIRT1/PINK1/Mitophagy Axis in Mice and in HK-2 Cells.

Groundwater resources are often contaminated by arsenic, which poses a serious threat to human and animal's health. Some studies have demonstrated that acute arsenic exposure could induce kidney injury because the kidney is a key target organ for toxicity, but the exact mechanism remains unclear. Hence, we investigated the effect of SIRT1-/PINK1-mediated mitophagy on NaAsO2-induced kidney injury in vivo and in vitro. In our study, NaAsO2 exposure obviously induced renal tubule injury and mitochondrial dysfunction. Meanwhile, NaAsO2 exposure could inhibit the mRNA/protein level of SIRT1 and activate the mitophagy-related mRNA/protein levels in the kidney of mice. In HK-2 cells, we also confirmed that NaAsO2-induced nephrotoxicity depended on the activation of mitophagy. Moreover, the activation of SIRT1 by resveratrol alleviated NaAsO2-induced acute kidney injury via the activation of mitophagy in vivo and in vitro. Interestingly, the inhibition of mitophagy by cyclosporin A (CsA) further exacerbated NaAsO2-induced nephrotoxicity and inflammation in HK-2 cells. Taken together, our study found that SIRT1-regulated PINK1-/Parkin-dependent mitophagy was implicated in NaAsO2-induced acute kidney injury. In addition, we confirmed that PINK1-/Parkin-dependent mitophagy played a protective role against NaAsO2-induced acute kidney injury. Therefore, activation of SIRT1 and mitophagy may represent a novel therapeutic target for the prevention and treatment of NaAsO2-induced acute renal injury.

[1]  Xu Shi,et al.  Combined negative effects of microplastics and plasticizer DEHP: The increased release of Nets delays wound healing in mice. , 2022, The Science of the total environment.

[2]  J. Kellum,et al.  Mitochondria ROS and mitophagy in acute kidney injury , 2022, Autophagy.

[3]  Dandan Liu,et al.  Melatonin mitigates aflatoxin B1‐induced liver injury via modulation of gut microbiota/intestinal FXR/liver TLR4 signaling axis in mice , 2022, Journal of pineal research.

[4]  Tong Xu,et al.  Oxidative stress mediated by the TLR4/NOX2 signalling axis is involved in polystyrene microplastic-induced uterine fibrosis in mice. , 2022, The Science of the total environment.

[5]  Weili,et al.  Low dose of arsenic exacerbates toxicity to mice and IPEC-J2 cells exposed with deoxynivalenol: Aryl hydrocarbon receptor and autophagy might be novel therapeutic targets. , 2022, The Science of the total environment.

[6]  Yunwei Wang,et al.  Regulation of SIRT1 and Its Roles in Inflammation , 2022, Frontiers in Immunology.

[7]  Wen-zhi Li,et al.  Adiponectin ameliorates lung ischemia–reperfusion injury through SIRT1-PINK1 signaling-mediated mitophagy in type 2 diabetic rats , 2021, Respiratory Research.

[8]  Yi Zhao,et al.  Lycopene mitigates DEHP-induced hepatic mitochondrial quality control disorder via regulating SIRT1/PINK1/mitophagy axis and mitochondrial unfolded protein response. , 2021, Environmental pollution.

[9]  Yongchao Wu,et al.  Liquiritigenin protects against arsenic trioxide-induced liver injury by inhibiting oxidative stress and enhancing mTOR-mediated autophagy. , 2021, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[10]  P. Ahmad,et al.  Fate of arsenic in living systems: Implications for sustainable and safe food chains. , 2021, Journal of hazardous materials.

[11]  I. Armando,et al.  Mitochondrial DNA-Mediated Inflammation in Acute Kidney Injury and Chronic Kidney Disease , 2021, Oxidative medicine and cellular longevity.

[12]  K. Mehmood,et al.  Arsenic and antimony co-induced nephrotoxicity via autophagy and pyroptosis through ROS-mediated pathway in vivo and in vitro. , 2021, Ecotoxicology and environmental safety.

[13]  M. Aschner,et al.  Sirtuins as molecular targets, mediators, and protective agents in metal-induced toxicity , 2021, Archives of Toxicology.

[14]  Wenlan Yu,et al.  Protective effects of curcumin on ATO-induced nephrotoxicity in ducks in relation to suppressed autophagy, apoptosis and dyslipidemia by regulating oxidative stress. , 2021, Ecotoxicology and environmental safety.

[15]  L. Bain,et al.  Arsenic exposure in drinking water reduces Lgr5 and secretory cell marker gene expression in mouse intestines. , 2021, Toxicology and applied pharmacology.

[16]  Kun Lu,et al.  The gut microbiome and arsenic-induced disease—iAs metabolism in mice , 2021, Current Environmental Health Reports.

[17]  B. B. Pereira,et al.  Arsenic exposure from groundwater: environmental contamination, human health effects, and sustainable solutions , 2021, Journal of toxicology and environmental health. Part B, Critical reviews.

[18]  C. Prakash,et al.  Mitochondrial Dysfunction in Arsenic-Induced Hepatotoxicity: Pathogenic and Therapeutic Implications , 2021, Biological Trace Element Research.

[19]  Zhiya Deng,et al.  SIRT1 attenuates sepsis-induced acute kidney injury via Beclin1 deacetylation-mediated autophagy activation , 2021, Cell Death & Disease.

[20]  Y. Liu,et al.  c-MYC-induced long noncoding RNA MEG3 aggravates kidney ischemia–reperfusion injury through activating mitophagy by upregulation of RTKN to trigger the Wnt/β-catenin pathway , 2021, Cell Death & Disease.

[21]  Wenfeng Ma,et al.  Dietary arsenic supplementation induces oxidative stress by suppressing nuclear factor erythroid 2-related factor 2 in the livers and kidneys of laying hens , 2020, Poultry science.

[22]  Z. Dong,et al.  The PINK1/PARK2/optineurin pathway of mitophagy is activated for protection in septic acute kidney injury , 2020, Redox biology.

[23]  B. Garcia,et al.  SIRT1 is downregulated by autophagy in senescence and aging , 2020, Nature Cell Biology.

[24]  Z. Dong,et al.  Autophagy in kidney homeostasis and disease , 2020, Nature Reviews Nephrology.

[25]  Shuang Liu,et al.  Arsenic induces hepatic insulin resistance via mtROS-NLRP3 inflammasome pathway. , 2020, Journal of hazardous materials.

[26]  V. Singh,et al.  Role of Silent Information Regulator 1 (SIRT1) in Regulating Oxidative Stress and Inflammation , 2020, Inflammation.

[27]  T. Hu,et al.  PINK1/Parkin-mediated mitophagy is involved in NaAsO2-induced apoptosis of human hepatic cells through activation of ERK signaling. , 2020, Toxicology in vitro : an international journal published in association with BIBRA.

[28]  W. Ding,et al.  Role and Mechanisms of Mitophagy in Liver Diseases , 2020, Cells.

[29]  R. Yao,et al.  Organelle-specific autophagy in inflammatory diseases: a potential therapeutic target underlying the quality control of multiple organelles , 2020, Autophagy.

[30]  R. Niu,et al.  Effect of arsenic and/or fluoride gestational exposure on renal autophagy in offspring mice. , 2020, Chemosphere.

[31]  D. Chan.  Mitochondrial Dynamics and Its Involvement in Disease. , 2020, Annual review of pathology.

[32]  R. Niu,et al.  Deregulation of autophagy is involved in nephrotoxicity of arsenite and fluoride exposure during gestation to puberty in rat offspring , 2019, Archives of Toxicology.

[33]  Z. Ni,et al.  PINK1-parkin pathway of mitophagy protects against contrast-induced acute kidney injury via decreasing mitochondrial ROS and NLRP3 inflammasome activation , 2019, Redox biology.

[34]  L. D. de Oliveira,et al.  Arsenic exposure intensifies glycogen nephrosis in diabetic rats , 2019, Environmental Science and Pollution Research.

[35]  Gang Qian,et al.  Activation of AMPK-dependent SIRT-1 by astragalus polysaccharide protects against ochratoxin A-induced immune stress in vitro and in vivo. , 2018, International journal of biological macromolecules.

[36]  P. Sil,et al.  Melatonin attenuates arsenic induced nephropathy via the regulation of oxidative stress and inflammatory signaling cascades in mice. , 2018, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[37]  P. Rada,et al.  SIRT1 Controls Acetaminophen Hepatotoxicity by Modulating Inflammation and Oxidative Stress. , 2017, Antioxidants & redox signaling.

[38]  P. Bhargava,et al.  Mitochondrial energetics in the kidney , 2017, Nature Reviews Nephrology.

[39]  C. Bridges,et al.  Chronic Kidney Disease and Exposure to Nephrotoxic Metals , 2017, International journal of molecular sciences.

[40]  Y. Isaka,et al.  Autophagy and kidney inflammation , 2017, Autophagy.

[41]  How-Ran Guo,et al.  Associations between arsenic in drinking water and the progression of chronic kidney disease: A nationwide study in Taiwan. , 2017, Journal of hazardous materials.

[42]  M. Lazarou,et al.  Deciphering the Molecular Signals of PINK1/Parkin Mitophagy. , 2016, Trends in cell biology.

[43]  Jianhua Zhang,et al.  Differential regulation of autophagy and mitophagy in pulmonary diseases. , 2016, American journal of physiology. Lung cellular and molecular physiology.

[44]  Lin Sun,et al.  Renoprotective approaches and strategies in acute kidney injury. , 2016, Pharmacology & therapeutics.

[45]  Steven P. Gygi,et al.  Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization , 2013, Nature.

[46]  D. Klionsky,et al.  SnapShot: Selective Autophagy , 2013, Cell.

[47]  N. Mukaida,et al.  MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice. , 2005, Toxicology and applied pharmacology.

[48]  B. Li,et al.  Acute arsenic exposure induces inflammatory responses and CD4+ T cell subpopulations differentiation in spleen and thymus with the involvement of MAPK, NF‐kB, and Nrf2 , 2017, Molecular immunology.

[49]  R. Youle,et al.  Mechanisms of mitophagy , 2010, Nature Reviews Molecular Cell Biology.

[50]  N. Mukaida,et al.  Interferon- (cid:1) Plays Protective Roles in Sodium Arsenite-Induced Renal Injury by Up-Regulating Intrarenal Multidrug Resistance-Associated Protein 1 Expression , 2006 .