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  1. Article ; Online: Endoplasmic Reticulum Protein TXNDC5 Interacts with PRDX6 and HSPA9 to Regulate Glutathione Metabolism and Lipid Peroxidation in the Hepatic AML12 Cell Line

    Seyed Hesamoddin Bidooki / Javier Sánchez-Marco / Roberto Martínez-Beamonte / Tania Herrero-Continente / María A. Navarro / María J. Rodríguez-Yoldi / Jesús Osada

    International Journal of Molecular Sciences, Vol 24, Iss 24, p

    2023  Volume 17131

    Abstract: Non-alcoholic fatty liver disease or steatosis is an accumulation of fat in the liver. Increased amounts of non-esterified fatty acids, calcium deficiency, or insulin resistance may disturb endoplasmic reticulum (ER) homeostasis, which leads to the ... ...

    Abstract Non-alcoholic fatty liver disease or steatosis is an accumulation of fat in the liver. Increased amounts of non-esterified fatty acids, calcium deficiency, or insulin resistance may disturb endoplasmic reticulum (ER) homeostasis, which leads to the abnormal accumulation of misfolded proteins, activating the unfolded protein response. The ER is the primary location site for chaperones like thioredoxin domain-containing 5 (TXNDC5). Glutathione participates in cellular oxidative stress, and its interaction with TXNDC5 in the ER may decrease the disulfide bonds of this protein. In addition, glutathione is utilized by glutathione peroxidases to inactivate oxidized lipids. To characterize proteins interacting with TXNDC5, immunoprecipitation and liquid chromatography–mass spectrometry were used. Lipid peroxidation, reduced glutathione, inducible phospholipase A 2 (iPLA 2 ) and hepatic transcriptome were assessed in the AML12 and TXNDC5-deficient AML12 cell lines. The results showed that HSPA9 and PRDX6 interact with TXNDC5 in AML12 cells. In addition, TXNDC5 deficiency reduced the protein levels of PRDX6 and HSPA9 in AML12. Moreover, lipid peroxidation, glutathione and iPLA 2 activities were significantly decreased in TXNDC5-deficient cells, and to find the cause of the PRDX6 protein reduction, proteasome suppression revealed no considerable effect on it. Finally, hepatic transcripts connected to PRDX6 and HSPA9 indicated an increase in the Dnaja3 , Mfn2 and Prdx5 and a decrease in Npm1 , Oplah , Gstp3 , Gstm6 , Gstt1 , Serpina1a , Serpina1b , Serpina3m , Hsp90aa1 and Rps14 mRNA levels in AML12 KO cells. In conclusion, the lipid peroxidation system and glutathione mechanism in AML12 cells may be disrupted by the absence of TXNDC5, a novel protein–protein interacting partner of PRDX6 and HSPA9.
    Keywords protein interaction ; TXNDC5 ; endoplasmic reticulum ; PRDX6 ; HSPA9 ; glutathione ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2023-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Hepatic galectin-3 is associated with lipid droplet area in non-alcoholic steatohepatitis in a new swine model

    Luis V. Herrera-Marcos / Roberto Martínez-Beamonte / Manuel Macías-Herranz / Carmen Arnal / Cristina Barranquero / Juan J. Puente-Lanzarote / Sonia Gascón / Tania Herrero-Continente / Gonzalo Gonzalo-Romeo / Víctor Alastrué-Vera / Dolores Gutiérrez-Blázquez / José M. Lou-Bonafonte / Joaquín C. Surra / María J. Rodríguez-Yoldi / Agustín García-Gil / Antonio Güemes / Jesús Osada

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 17

    Abstract: Abstract Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, ... ...

    Abstract Abstract Non-alcoholic fatty liver disease (NAFLD) is currently a growing epidemic disease that can lead to cirrhosis and hepatic cancer when it evolves into non-alcoholic steatohepatitis (NASH), a gap not well understood. To characterize this disease, pigs, considered to be one of the most similar to human experimental animal models, were used. To date, all swine-based settings have been carried out using rare predisposed breeds or long-term experiments. Herein, we fully describe a new experimental swine model for initial and reversible NASH using cross-bred animals fed on a high saturated fat, fructose, cholesterol, cholate, choline and methionine-deficient diet. To gain insight into the hepatic transcriptome that undergoes steatosis and steatohepatitis, we used RNA sequencing. This process significantly up-regulated 976 and down-regulated 209 genes mainly involved in cellular processes. Gene expression changes of 22 selected transcripts were verified by RT-qPCR. Lipid droplet area was positively associated with CD68, GPNMB, LGALS3, SLC51B and SPP1, and negatively with SQLE expressions. When these genes were tested in a second experiment of NASH reversion, LGALS3, SLC51B and SPP1 significantly decreased their expression. However, only LGALS3 was associated with lipid droplet areas. Our results suggest a role for LGALS3 in the transition of NAFLD to NASH.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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