AMPK/PPAR-γ/NF-κB axis participates in ROS-mediated apoptosis and autophagy caused by cadmium in pig liver

Wang, Huan; Wang, Anqi; Wang, Xinqiao; Zeng, Xiangyin; Xing, Houjuan

doi:10.1016/j.envpol.2021.118659

Cited by 55 publications

(19 citation statements)

References 70 publications

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“…Furthermore, the analysis of the KEGG pathway showed that a large number of host proteins interacting with M protein are mainly involved in the ribosomal pathway, apoptosis, autophagy, cell cycle, adenosine monophosphate-activated protein kinase (AMPK) signal pathway and multiple metabolic pathways, PI3K-AKT signal pathway, exocytosis, proteasome, splice body signal pathway, and other important signal pathways in the host body. It is known that the AMPK signal pathway is linked to autophagy and apoptosis (Wang et al, 2022), so there is a possibility that M protein may regulate autophagy and apoptosis by targeting key proteins in the AMPK signal pathway. Interestingly, some host proteins are associated with other viruses, such as Epstein-Barr (EB) virus, hepatitis B, human papillomavirus, hepatitis C, FIGURE 5 | Validation of M-host protein interactions.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Interaction Network Between Host Protein and M Protein of Swine Acute Diarrhea Syndrome Coronavirus

Cao

et al. 2022

Front. Microbiol.

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Swine acute diarrhea syndrome coronavirus (SADS-CoV) is an enterovirus that can cause acute diarrhea and death in piglets and cause serious economic losses to the pig industry. SADS-CoV membrane (M) protein mainly plays a key role in biological processes, such as virus assembly, budding, and host innate immune regulation. Understanding the interaction between M protein and host proteins is very important to define the molecular mechanism of cells at the protein level and to understand specific cellular physiological pathways. In this study, 289 host proteins interacting with M protein were identified by glutathione-S-transferase (GST) pull-down combined with liquid chromatography-mass spectrometry (LC-MS/MS), and the protein-protein interaction (PPI) network was established by Gene Ontology (GO) terms and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathways analysis. Results showed that SADS-CoV M protein was mainly associated with the host metabolism, signal transduction, and innate immunity. The Co-Immunoprecipitation (CO-IP) validation results of six randomly selected proteins, namely, Rab11b, voltage-dependent anion-selective channel 1 (VDAC1), Ribosomal Protein L18 (RPL18), RALY, Ras Homolog Family Member A (RHOA), and Annexin A2 (ANXA2), were consistent with LC-MS results. In addition, overexpression of RPL18 and PHOA significantly promoted SADS-CoV replication, while overexpression of RALY antagonized viral replication. This work will help to clarify the function of SADS-CoV M protein in the life cycle of SADS-CoV.

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Section: Discussionmentioning

confidence: 99%

Analysis of Interaction Network Between Host Protein and M Protein of Swine Acute Diarrhea Syndrome Coronavirus

Cao

et al. 2022

Front. Microbiol.

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“…Cd-decreased BIRC3 also induces apoptosis in the HK-2 cells [ 8 ]. PPARγ is involved in Cd-induced apoptosis and oxidative stress in renal epithelial cells and hepatocytes [ 44 , 45 ]. In the rat heart cells, DHA (docosahexaenoic acid), which acts as a ligand for PPARδ, has been reported to promote apoptotic cell death, increase caspase-3 activity, and reduce Akt phosphorylation via PPARδ [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Cadmium Toxicity Is Regulated by Peroxisome Proliferator-Activated Receptor δ in Human Proximal Tubular Cells

Mori

Lee

Tokumoto

et al. 2022

IJMS

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Cadmium (Cd) is a toxic heavy metal that is widely present in the environment. Renal proximal tubule disorder is the main symptom of Cd chronic poisoning. Our previous study demonstrated that Cd inhibits the total activities of peroxisome proliferator-activated receptor (PPAR) transcription factors in human and rat proximal tubular cells. In this study, we investigated the involvement of PPAR in Cd renal toxicity using the HK-2 human proximal tubular cell line. Among PPAR isoform genes, only PPARD knockdown significantly showed resistance to Cd toxicity in HK-2 cells. The transcriptional activity of PPARδ was decreased not only by PPARD knockdown but also by Cd treatment. DNA microarray analysis showed that PPARD knockdown changed the expression of apoptosis-related genes in HK-2 cells. PPARD knockdown decreased apoptosis signals and caspase-3 activity induced by Cd treatment. PPARD knockdown did not affect the intracellular Cd level after Cd treatment. These results suggest that PPARδ plays a critical role in the modification of susceptibility to Cd renal toxicity and that the apoptosis pathway may be involved in PPARδ-related Cd toxicity.

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“…PPAR-γ, which could inhibit cell-programmed apoptosis, is an upstream regulatory element of cyclooxygenase 2[ 52 ]. The expression level of PPAR-γ was suppressed in the porcine kidney under cadmium exposure and the typical characteristics of apoptosis were observed [ 65 ]. So far, it has been demonstrated that cadmium could induce the apoptosis of pancreas cells in chickens by suppressing the PI3K/Akt/PPAR-γ pathway while the pro-apoptosis factors were up-regulated [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Selenium Mitigates Ammonia-Induced Neurotoxicity by Suppressing Apoptosis, Immune Imbalance, and Gut Microbiota-Driven Metabolic Disturbance in Fattening Pigs

Wang

Xing

et al. 2022

Biol Trace Elem Res

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Ammonia could be regarded as one detrimental pollutant with an acrid smell in livestock sheds. So far, the pig breeding industry became the main source of atmospheric ammonia. Previous literature demonstrated that excessive ammonia inhalation might cause a series of physiological damage to multiple organs. Unfortunately, the toxicity mechanisms of gaseous ammonia to the porcine nervous system need further research to elucidate. Selenium (Se) involves in many essential physiological processes and has a mitigative effect on the exogenous toxicant. There were scant references that corroborated whether organic Se could intervene in the underlying toxicity of ammonia to the hypothalamus. In the present study, multi-omics tools, ethology, and molecular biological techniques were performed to clarify the detailed mechanisms of relaxation effects of L-selenomethionine on ammonia poisoning. Our results showed that ammonia inhalation caused the clinical symptoms and the increment of positive apoptosis rate in the hypothalamus with the dysfunction of mitochondrial dynamics factors, while obvious mitochondria structure defects were observed. In parallel, the inflammation medium levels and gut microbes-driven metabolism function were altered to mediate the neurotoxicity in fattening pigs through the initiation of inflammation development. Interestingly, L-selenomethionine could attenuate ammonia toxicity by activating the PI3K/Akt/PPAR-γ pathway to inhibit the mitochondria-mediated apoptosis process, blocking the abnormal immune response and the accumulation of reactive oxygen species in the nucleus. Meanwhile, Se could enhance the production performance of fattening sows. Taken together, our study verified the novel hypothesis for the toxicity identification of aerial ammonia and provided a therapeutic strategy for the treatment of occupational poisoning. Supplementary Information The online version contains supplementary material available at 10.1007/s12011-022-03434-w.

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AMPK/PPAR-γ/NF-κB axis participates in ROS-mediated apoptosis and autophagy caused by cadmium in pig liver

Cited by 55 publications

References 70 publications

Analysis of Interaction Network Between Host Protein and M Protein of Swine Acute Diarrhea Syndrome Coronavirus

Analysis of Interaction Network Between Host Protein and M Protein of Swine Acute Diarrhea Syndrome Coronavirus

Cadmium Toxicity Is Regulated by Peroxisome Proliferator-Activated Receptor δ in Human Proximal Tubular Cells

Selenium Mitigates Ammonia-Induced Neurotoxicity by Suppressing Apoptosis, Immune Imbalance, and Gut Microbiota-Driven Metabolic Disturbance in Fattening Pigs

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