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  1. Article ; Online: Protein kinase A signals apoptotic activation in glucose-deprived hepatocytes: participation of reactive oxygen species.

    Ferretti, Anabela C / Mattaloni, Stella M / Ochoa, Justina E / Larocca, María C / Favre, Cristián

    Apoptosis : an international journal on programmed cell death

    2012  Volume 17, Issue 5, Page(s) 475–491

    Abstract: Glucose deprivation entails oxidative stress and apoptosis in diverse cell types. Liver tissue shows high tolerance to nutritional stress, however regulation of survival in normal hepatocytes subjected to glucose restriction is unclear. We assessed the ... ...

    Abstract Glucose deprivation entails oxidative stress and apoptosis in diverse cell types. Liver tissue shows high tolerance to nutritional stress, however regulation of survival in normal hepatocytes subjected to glucose restriction is unclear. We assessed the survival response of cultured hepatocytes subjected to glucose deprivation and analyzed the putative participation of protein kinase A (PKA) in this response. Six hours glucose deprivation induced a PKA dependent activation of apoptosis in cultured hepatocytes, without having an impact on non apoptotic death. Apoptotic activation associated to glucose restriction was secondary to an imbalance in cellular reactive oxygen species (ROS). In this condition, PKA inhibition led to an early prevention in mitochondrial ROS production and a late increase in scavenging enzymes transcript levels. These results supported the hypothesis that PKA could modulate glucose deprivation induced apoptotic activation by conditioning mitochondrial ROS production during glucose fasting. We presented additional evidence sustaining this model: First, glucose withdrawal led to a 95% increase in mitochondrial cAMP levels in cultured hepatocytes; second, activation of PKA significantly augmented hepatic mitochondrial ROS generation, whereas PKA inhibition elicited the opposite effect. Mitochondrial PKA signaling, previously proposed as an autonomic pathway adjusting respiration rate, emerges as a mechanism of controlling cell survival during glucose restriction.
    MeSH term(s) Animals ; Apoptosis ; Caspase 3/metabolism ; Catalase/genetics ; Catalase/metabolism ; Cell Survival ; Cells, Cultured ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cytochromes c/metabolism ; Cytosol/metabolism ; Glucose/deficiency ; Hepatocytes/enzymology ; Hepatocytes/physiology ; Isoquinolines/pharmacology ; L-Lactate Dehydrogenase/metabolism ; Male ; Mitochondria/metabolism ; Oxidative Stress ; Protein Transport ; Rats ; Rats, Wistar ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Sulfonamides/pharmacology ; Superoxide Dismutase/genetics ; Superoxide Dismutase/metabolism ; Superoxide Dismutase-1 ; bcl-2-Associated X Protein/metabolism
    Chemical Substances Bax protein, rat ; Isoquinolines ; Reactive Oxygen Species ; Sulfonamides ; bcl-2-Associated X Protein ; Cytochromes c (9007-43-6) ; Cyclic AMP (E0399OZS9N) ; L-Lactate Dehydrogenase (EC 1.1.1.27) ; Catalase (EC 1.11.1.6) ; Sod1 protein, rat (EC 1.15.1.1) ; Superoxide Dismutase (EC 1.15.1.1) ; Superoxide Dismutase-1 (EC 1.15.1.1) ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11) ; Casp3 protein, rat (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) ; Glucose (IY9XDZ35W2) ; N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide (M876330O56)
    Language English
    Publishing date 2012-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1452360-7
    ISSN 1573-675X ; 1360-8185
    ISSN (online) 1573-675X
    ISSN 1360-8185
    DOI 10.1007/s10495-012-0697-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: AKAP350 Is involved in the development of apical "canalicular" structures in hepatic cells HepG2.

    Mattaloni, Stella M / Kolobova, Elena / Favre, Cristián / Marinelli, Raúl A / Goldenring, James R / Larocca, Maria C

    Journal of cellular physiology

    2011  Volume 227, Issue 1, Page(s) 160–171

    Abstract: Hepatocytes are epithelial cells whose apical poles constitute the bile canaliculi. The establishment and maintenance of canalicular poles is a finely regulated process that dictates the efficiency of primary bile secretion. Protein kinase A (PKA) ... ...

    Abstract Hepatocytes are epithelial cells whose apical poles constitute the bile canaliculi. The establishment and maintenance of canalicular poles is a finely regulated process that dictates the efficiency of primary bile secretion. Protein kinase A (PKA) modulates this process at different levels. AKAP350 is an A-kinase anchoring protein that scaffolds protein complexes involved in modulating the dynamic structures of the Golgi apparatus and microtubule cytoskeleton, facilitating microtubule nucleation at this organelle. In this study, we evaluated whether AKAP350 is involved in the development of bile canaliculi-like structures in hepatocyte derived HepG2 cells. We found that AKAP350 recruits PKA to the centrosomes and Golgi apparatus in HepG2 cells. De-localization of AKAP350 from these organelles led to reduced apical cell polarization. A decrease in AKAP350 expression inhibited the formation of canalicular structures and impaired F-actin organization at canalicular poles. Furthermore, loss of AKAP350 expression led to diminished polarized expression of the p-glycoprotein (MDR1/ABCB1) at the apical "canalicular" membrane. AKAP350 knock down effects on canalicular structures formation and actin organization could be mimicked by inhibition of Golgi microtubule nucleation by depletion of CLIP associated proteins (CLASPs). Our data reveal that AKAP350 participates in mechanisms which determine the development of canalicular structures as well as accurate canalicular expression of distinct proteins and actin organization, and provide evidence on the involvement of Golgi microtubule nucleation in hepatocyte apical polarization.
    MeSH term(s) A Kinase Anchor Proteins/metabolism ; Actin Cytoskeleton/metabolism ; Actin Cytoskeleton/ultrastructure ; Bile Canaliculi/metabolism ; Bile Canaliculi/ultrastructure ; Cell Polarity/physiology ; Centrosome/metabolism ; Centrosome/ultrastructure ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cytoskeletal Proteins/metabolism ; Fluorescent Antibody Technique ; Golgi Apparatus/metabolism ; Golgi Apparatus/ultrastructure ; Hep G2 Cells ; Hepatocytes/metabolism ; Hepatocytes/ultrastructure ; Humans ; Immunoblotting ; Microscopy, Confocal ; Microscopy, Fluorescence
    Chemical Substances A Kinase Anchor Proteins ; AKAP9 protein, human ; Cytoskeletal Proteins ; Cyclic AMP-Dependent Protein Kinases (EC 2.7.11.11)
    Language English
    Publishing date 2011-03-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 3116-1
    ISSN 1097-4652 ; 0021-9541
    ISSN (online) 1097-4652
    ISSN 0021-9541
    DOI 10.1002/jcp.22713
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Centrosomal AKAP350 modulates the G

    Mattaloni, Stella M / Ferretti, Anabela C / Tonucci, Facundo M / Favre, Cristián / Goldenring, James R / Larocca, M Cecilia

    Cellular logistics

    2013  Volume 3, Issue 1, Page(s) e26331

    Abstract: AKAP350 (AKAP450/AKAP9/CG-NAP) is an A-kinase anchoring protein, which recruits multiple signaling proteins to the Golgi apparatus and the centrosomes. Several proteins recruited to the centrosomes by this scaffold participate in the regulation of the ... ...

    Abstract AKAP350 (AKAP450/AKAP9/CG-NAP) is an A-kinase anchoring protein, which recruits multiple signaling proteins to the Golgi apparatus and the centrosomes. Several proteins recruited to the centrosomes by this scaffold participate in the regulation of the cell cycle. Previous studies indicated that AKAP350 participates in centrosome duplication. In the present study we specifically assessed the role of AKAP350 in the progression of the cell cycle. Our results showed that interference with AKAP350 expression inhibits G
    Language English
    Publishing date 2013-09-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2682440-1
    ISSN 2159-2799 ; 2159-2780
    ISSN (online) 2159-2799
    ISSN 2159-2780
    DOI 10.4161/cl.26331
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Genotyping approach for non-invasive foetal RHD detection in an admixed population.

    Boggione, Carolina Trucco / Luján Brajovich, Melina E / Mattaloni, Stella M / Di Mónaco, René A / García Borrás, Silvia E / Biondi, Claudia S / Cotorruelo, Carlos M

    Blood transfusion = Trasfusione del sangue

    2016  Volume 15, Issue 1, Page(s) 66–73

    Abstract: Background: Non-invasive foetal RHD genotyping can predict haemolytic disease of the foetus and the newborn in pregnancies with anti-D alloantibodies and also avoid antenatal anti-D prophylaxis in pregnant women carrying an RHD negative foetus. ... ...

    Abstract Background: Non-invasive foetal RHD genotyping can predict haemolytic disease of the foetus and the newborn in pregnancies with anti-D alloantibodies and also avoid antenatal anti-D prophylaxis in pregnant women carrying an RHD negative foetus. Considering that the Argentine genetic background is the result of generations of intermixing between several ethnic groups, we evaluated the diagnostic performance of a non-invasive foetal RHD determination strategy to guide targeted antenatal RhD immunoprophylaxis. This algorithm is based on the analysis of four regions of the RHD gene in cell-free foetal DNA in maternal plasma and maternal and paternal RHD genotyping.
    Materials and methods: DNA from 298 serologically D negative pregnant women between 19-28 weeks gestation were RHD genotyped. Foetal RHD status was determined by real-time PCR in 296 maternal plasma samples. In particular cases, RHDΨ and RHD-CE-D
    Results: Of the 298 maternal samples, 288 were D-/RHD- and 10 D-/RHD+ (2 RHD*DAR; 5 RHD-CE-D
    Discussion: The protocol used for non-invasive prenatal RHD genotyping proved to be suitable to determine foetal RHD status in our admixed population. The knowledge of the genetic background of the population under study and maternal and paternal molecular analysis can reduce the number of inconclusive results when investigating foetal RHD status.
    MeSH term(s) DNA/blood ; DNA/genetics ; Female ; Fetal Blood/immunology ; Fetus/immunology ; Fetus/metabolism ; Genetic Variation ; Genotype ; Genotyping Techniques/methods ; Gestational Age ; Humans ; Immunotherapy ; Male ; Pregnancy ; Prenatal Diagnosis ; Rh-Hr Blood-Group System/blood ; Rh-Hr Blood-Group System/genetics ; Rh-Hr Blood-Group System/immunology
    Chemical Substances Rh-Hr Blood-Group System ; DNA (9007-49-2)
    Language English
    Publishing date 2016-03-21
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 2135732-8
    ISSN 1723-2007 ; 0041-1787
    ISSN 1723-2007 ; 0041-1787
    DOI 10.2450/2016.0228-15
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Molecular structures identified in serologically D- samples of an admixed population.

    Trucco Boggione, Carolina / Luján Brajovich, Melina E / Tarragó, Marcel / Mattaloni, Stella M / Biondi, Claudia S / Muñiz-Díaz, Eduardo / Nogués, Núria / Cotorruelo, Carlos M

    Transfusion

    2014  Volume 54, Issue 10, Page(s) 2456–2462

    Abstract: Background: The D- phenotype is mainly caused by the complete deletion of the RHD gene in Caucasians. However, a plethora of allelic variants have been described among D- individuals from different ethnic groups.: Study design and methods: A cohort ... ...

    Abstract Background: The D- phenotype is mainly caused by the complete deletion of the RHD gene in Caucasians. However, a plethora of allelic variants have been described among D- individuals from different ethnic groups.
    Study design and methods: A cohort of 1314 routine serologically D- samples from white Argentineans was studied by molecular methods.
    Results: Among the 1314 D- samples, 2.1% showed RHD-specific amplifications. One hybrid Rhesus box was detected in all D-/RHD+ samples, suggesting a hemizygous status. The RHDΨ was found in 0.7% of rr samples while DEL and null variants were detected in 16.7% of the D- samples expressing C and/or E antigens. The variants associated with the C antigen were seven RHD-CE-D(s) , two RHD(1-2)-CE(2-9)-D(10), two previously unreported RHD(329T>C)-CE(3-9)-D null alleles, one RHD(M295I), and one new RHCE(1-2)-RHD(3361del11 -10) null allele whereas those associated with the E antigen were five RHD(46T>C) and one novel RHD(581insG) null allele responsible for a premature stop codon.
    Conclusions: The prevalence of D-/RHD+ samples is higher than that observed in Europeans. More than 50% of the RHD alleles found were represented by RHDψ and RHD-CE-D(s) showing the African contribution to the genetic pool of the admixed population analyzed. Interestingly, three new alleles were found, two of them being hybrid structures between previously described RHD variants recombined with RHCE sequences. The knowledge of the RHD allele repertoire in our population allowed the implementation of reliable typing and transfusion strategies for a better management of patients and pregnant women.
    MeSH term(s) African Continental Ancestry Group/genetics ; Alleles ; Argentina/epidemiology ; Blood Donors/statistics & numerical data ; Cohort Studies ; European Continental Ancestry Group/genetics ; Female ; Gene Frequency ; Humans ; Male ; Pedigree ; Phenotype ; Rh-Hr Blood-Group System/blood ; Rh-Hr Blood-Group System/genetics ; Rh-Hr Blood-Group System/immunology ; Sequence Analysis, DNA ; Sequence Deletion ; Serologic Tests
    Chemical Substances Rh-Hr Blood-Group System ; Rho(D) antigen
    Language English
    Publishing date 2014-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.12691
    Database MEDical Literature Analysis and Retrieval System OnLINE

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