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  1. Article ; Online: Dynamics of Mitochondrial Proteome and Acetylome in Glioblastoma Cells with Contrasting Metabolic Phenotypes.

    Fernández-Coto, Diana Lashidua / Gil, Jeovanis / Ayala, Guadalupe / Encarnación-Guevara, Sergio

    International journal of molecular sciences

    2024  Volume 25, Issue 6

    Abstract: Glioblastoma, a type of cancer affecting the central nervous system, is characterized by its poor prognosis and the dynamic alteration of its metabolic phenotype to fuel development and progression. Critical to cellular metabolism, mitochondria play a ... ...

    Abstract Glioblastoma, a type of cancer affecting the central nervous system, is characterized by its poor prognosis and the dynamic alteration of its metabolic phenotype to fuel development and progression. Critical to cellular metabolism, mitochondria play a pivotal role, where the acetylation of lysine residues on mitochondrial enzymes emerges as a crucial regulatory mechanism of protein function. This post-translational modification, which negatively impacts the mitochondrial proteome's functionality, is modulated by the enzyme sirtuin 3 (SIRT3). Aiming to elucidate the regulatory role of SIRT3 in mitochondrial metabolism within glioblastoma, we employed high-resolution mass spectrometry to analyze the proteome and acetylome of two glioblastoma cell lines, each exhibiting distinct metabolic behaviors, following the chemical inhibition of SIRT3. Our findings reveal that the protein synthesis machinery, regulated by lysine acetylation, significantly influences the metabolic phenotype of these cells. Moreover, we have shed light on potential novel SIRT3 targets, thereby unveiling new avenues for future investigations. This research highlights the critical function of SIRT3 in mitochondrial metabolism and its broader implications for cellular energetics. It also provides a comparative analysis of the proteome and acetylome across glioblastoma cell lines with opposing metabolic phenotypes.
    MeSH term(s) Humans ; Sirtuin 3/metabolism ; Proteome/metabolism ; Lysine/metabolism ; Glioblastoma/metabolism ; Mitochondria/metabolism ; Protein Processing, Post-Translational ; Phenotype ; Acetylation ; Mitochondrial Proteins/metabolism
    Chemical Substances Sirtuin 3 (EC 3.5.1.-) ; Proteome ; Lysine (K3Z4F929H6) ; Mitochondrial Proteins
    Language English
    Publishing date 2024-03-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms25063450
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer

    Fernández-Coto, Diana Lashidua / Alfonso Mendez-Tenorio / Ana Silvia Arenas-Linares / Angélica Hernández / Eva Hernández-Márquez / Guadalupe Ayala / Ivone Castro-Romero / Jeovanis Gil / Miguel Ángel Sanchez-Aleman / Roberto Herrera-Goepfert / Sergio Encarnación-Guevara / Valia Tletzalli Calderon-Sosa

    Journal of proteomics. 2018,

    2018  

    Abstract: Gastric cancer is one of the most aggressive malignancies affecting humankind. With almost a million cases globally, it sits in fifth position in terms of incidence, and third in terms of mortality. The progression of this disease is slow, with prolonged ...

    Abstract Gastric cancer is one of the most aggressive malignancies affecting humankind. With almost a million cases globally, it sits in fifth position in terms of incidence, and third in terms of mortality. The progression of this disease is slow, with prolonged and sequential precancerous stages including chronic gastritis, intestinal metaplasia, dysplasia, and finally gastric cancer. Here we used the iTRAQ approach combined with high-resolution mass spectrometry analysis to describe the spectrum of the gastric cancer cascade. Biopsies from three stages: chronic gastritis, intestinal metaplasia, and gastric adenocarcinoma, were selected for analysis by quantitative proteomics. We identified and reported quantitative data for 3914 different proteins quantified with high confidence, uncovering pathways and processes dysregulated between the different stages. Intestinal metaplasia is characterized by the down-regulation of ribosomal proteins, with overexpression of cell survival proteins such as GSTP1 and EPCAM. The transformation to gastric cancer involves overexpression of the DNA replication and the spliceosome pathways. The impairment of mitochondrial pathways was correlated with down-regulation of SIRT3 and SIRT5, and overexpression of enzymes supporting the glycolytic phenotype, such as HK3 and PCK2. Several proteins found dysregulated during the progression of gastric cancer have potential to be used as specific biomarkers and/or therapeutic targets.
    Keywords adenocarcinoma ; biomarkers ; biopsy ; cell viability ; DNA replication ; enzymes ; gastritis ; gene expression regulation ; gene overexpression ; glycolysis ; intestines ; mass spectrometry ; metaplasia ; mitochondria ; mortality ; phenotype ; proteomics ; ribosomal proteins ; spliceosomes ; stomach neoplasms
    Language English
    Size p. .
    Publishing place Elsevier B.V.
    Document type Article
    Note Pre-press version
    ZDB-ID 2400835-7
    ISSN 1876-7737 ; 1874-3919
    ISSN (online) 1876-7737
    ISSN 1874-3919
    DOI 10.1016/j.jprot.2018.07.013
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer.

    Fernández-Coto, Diana Lashidua / Gil, Jeovanis / Hernández, Angélica / Herrera-Goepfert, Roberto / Castro-Romero, Ivone / Hernández-Márquez, Eva / Arenas-Linares, Ana Silvia / Calderon-Sosa, Valia Tletzalli / Sanchez-Aleman, Miguel Ángel / Mendez-Tenorio, Alfonso / Encarnación-Guevara, Sergio / Ayala, Guadalupe

    Journal of proteomics

    2018  Volume 186, Page(s) 15–27

    Abstract: Gastric cancer is one of the most aggressive malignancies affecting humankind. With almost a million cases globally, it sits in fifth position in terms of incidence, and third in terms of mortality. The progression of this disease is slow, with prolonged ...

    Abstract Gastric cancer is one of the most aggressive malignancies affecting humankind. With almost a million cases globally, it sits in fifth position in terms of incidence, and third in terms of mortality. The progression of this disease is slow, with prolonged and sequential precancerous stages including chronic gastritis, intestinal metaplasia, dysplasia, and finally gastric cancer. Here we used the iTRAQ approach combined with high-resolution mass spectrometry analysis to describe the spectrum of the gastric cancer cascade. Biopsies from three stages: chronic gastritis, intestinal metaplasia, and gastric adenocarcinoma, were selected for analysis by quantitative proteomics. We identified and reported quantitative data for 3914 different proteins quantified with high confidence, uncovering pathways and processes dysregulated between the different stages. Intestinal metaplasia is characterized by the down-regulation of ribosomal proteins, with overexpression of cell survival proteins such as GSTP1 and EPCAM. The transformation to gastric cancer involves overexpression of the DNA replication and the spliceosome pathways. The impairment of mitochondrial pathways was correlated with down-regulation of SIRT3 and SIRT5, and overexpression of enzymes supporting the glycolytic phenotype, such as HK3 and PCK2. Several proteins found dysregulated during the progression of gastric cancer have potential to be used as specific biomarkers and/or therapeutic targets.
    MeSH term(s) Adenocarcinoma/pathology ; Biomarkers/analysis ; Biopsy ; Disease Progression ; Gastritis/pathology ; Humans ; Metaplasia/pathology ; Precancerous Conditions/diagnosis ; Precancerous Conditions/pathology ; Proteins/analysis ; Proteins/metabolism ; Proteomics/methods ; Stomach Neoplasms/chemistry ; Stomach Neoplasms/diagnosis
    Chemical Substances Biomarkers ; Proteins
    Language English
    Publishing date 2018-07-23
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2400835-7
    ISSN 1876-7737 ; 1874-3919
    ISSN (online) 1876-7737
    ISSN 1874-3919
    DOI 10.1016/j.jprot.2018.07.013
    Database MEDical Literature Analysis and Retrieval System OnLINE

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