CRIS

Permanent URI for this communityhttps://investigadores.udd.cl/handle/123456789/1

Browse

Settings

Language: search.filters.language.EnglishSubject: search.filters.subject.enzyme activity

Search Results

Now showing 1 - 2 of 2
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    A Mouse Systems Genetics Approach Reveals Common and Uncommon Genetic Modifiers of Hepatic Lysosomal Enzyme Activities and Glycosphingolipids
    (2023)
    Anyelo Durán
    ;
    David A. Priestman
    ;
    Macarena Las Las Heras
    ;
    Boris Rebolledo-Jaramillo
    ;
    Valeria Olguín
    <jats:p>Identification of genetic modulators of lysosomal enzyme activities and glycosphingolipids (GSLs) may facilitate the development of therapeutics for diseases in which they participate, including Lysosomal Storage Disorders (LSDs). To this end, we used a systems genetics approach: we measured 11 hepatic lysosomal enzymes and many of their natural substrates (GSLs), followed by modifier gene mapping by GWAS and transcriptomics associations in a panel of inbred strains. Unexpectedly, most GSLs showed no association between their levels and the enzyme activity that catabolizes them. Genomic mapping identified 30 shared predicted modifier genes between the enzymes and GSLs, which are clustered in three pathways and are associated with other diseases. Surprisingly, they are regulated by ten common transcription factors, and their majority by miRNA-340p. In conclusion, we have identified novel regulators of GSL metabolism, which may serve as therapeutic targets for LSDs and may suggest the involvement of GSL metabolism in other pathologies.</jats:p>
      1
  • Loading...
    Thumbnail Image
    Some of the metrics are blocked by your 
    consent settings
    Item type:Publication,
    Cancer History Avoids the Increase of Senescence Markers in Peripheral Cells of Amnestic Mild Cognitive Impaired Patients
    (2023)
    Carol D. SanMartín
    ;
    Felipe Salech
    ;
    Daniela Paz Ponce
    ;
    Jorge Concha-Cerda
    ;
    Esteban Romero-Hernández
    <jats:p>Epidemiological studies show that having a history of cancer protects from the development of Alzheimer’s Disease (AD), and vice versa, AD protects from cancer. The mechanism of this mutual protection is unknown. We have reported that the peripheral blood mononuclear cells (PBMC) of amnestic cognitive impairment (aMCI) and Alzheimer’s Disease (AD) patients have increased susceptibility to oxidative cell death compared to control subjects, and from the opposite standpoint a cancer history is associated with increased resistance to oxidative stress cell death in PBMCs, even in those subjects who have cancer history and aMCI (Ca + aMCI). Cellular senescence is a regulator of susceptibility to cell death and has been related to the pathophysiology of AD and cancer. Recently, we showed that cellular senescence markers can be tracked in PBMCs of aMCI patients, so we here investigated whether these senescence markers are dependent on having a history of cancer. Senescence-associated βeta-galactosidase (SA-β-Gal) activity, G0-G1 phase cell-cycle arrest, p16 and p53 were analyzed by flow cytometry; phosphorylated H2A histone family member X (γH2AX) by immunofluorescence; IL-6 and IL-8 mRNA by qPCR; and plasmatic levels by ELISA. Senescence markers that were elevated in PBMCs of aMCI patients, such as SA-β-Gal, Go-G1 arrested cells, IL-6 and IL-8 mRNA expression, and IL-8 plasmatic levels, were decreased in PBMCs of Ca + aMCI patients to levels similar to those of controls or of cancer survivors without cognitive impairment, suggesting that cancer in the past leaves a fingerprint that can be peripherally traceable in PBMC samples. These results support the hypothesis that the senescence process might be involved in the inverse association between cancer and AD.</jats:p>
      3