TY  - JOUR
AB  - Transient receptor potential channel subfamily M member 7 (TRPM7) regulates cellular and systemic Mg2+ homeostasis through its channel domain and induces protein phosphorylation via its kinase domain. We recently found that mice with selective deletion of Trpm7 in β-cells develop glucose intolerance and declines in insulin secretion, primarily due to the impaired enzymatic activity of this protein. Accumulating evidence suggests that Mg2+ supplementation effectively mitigates the detrimental effects of TRPM7 disruption in various cell types. However, the impact of Mg2+ supplementation on metabolic impairments caused by TRPM7 inactivation remains unclear. In the present study, we found that Mg2+ supplementation significantly ameliorates glucose intolerance observed in high-fat-fed TRPM7 kinase-deficient mice (Trpm7R/R). However, our ex vivo analysis of islets isolated from Trpm7R/R mice revealed that Mg2+ supplementation does not enhance glucose-induced insulin secretion. Instead, the improvement appears to be partially driven by enhanced insulin sensitivity and increased β-cell proliferation. The pharmacological analysis in MIN6 cells showed that inhibiting TRPM7 with either NS8593 or VER155008 disrupts β-cell proliferation. These effects mimicked the phenotype seen in Trpm7R/R mice. We attribute this impairment to diminished ERK1/2 signaling, which suppressed PDX1 expression, while Mg2+ supplementation in vitro partially restored ERK1/2 phosphorylation levels. Collectively, Mg2+ supplementation enhances glucose metabolism in Trpm7R/R mice and mitigates the ERK1/2 signaling disruptions and proliferation arrest induced by TRPM7 inactivation in vitro. These findings provide compelling evidence that Mg2+ supplementation can reverse the adverse metabolic and cellular phenotypes associated with the loss of TRPM7 function.
AU  - Boulassel, S.*
AU  - Schreier, P.C.F.*
AU  - Melyshi, A.M.*
AU  - Berger, J.*
AU  - Reinach, P.S.*
AU  - Jacob, K.*
AU  - Boekhoff, I.*
AU  - Breit, A.*
AU  - Müller, T.D.
AU  - Zierler, S.*
AU  - Gudermann, T.*
AU  - Khajavi, N.*
C1  - 74200
C2  - 57393
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
TI  - Mg2+ supplementation mitigates metabolic deficits associated with TRPM7 disruption.
JO  - J. Cell. Physiol.
VL  - 240
IS  - 4
PB  - Wiley
PY  - 2025
SN  - 0021-9541
ER  - 

TY  - JOUR
AB  - Radiation exposure can evoke cellular stress responses. Emerging recognition that long non-coding RNAs (lncRNAs) act as regulators of gene expression has broadened the spectra of molecules controlling the genomic landscape upon alterations in environmental conditions. Knowledge of the mechanisms responding to low dose irradiation (LDR) exposure is very limited yet most likely involve subtle ancillary molecular pathways other than those protecting the cell from direct cellular damage. The discovery that transcription of the lncRNA PARTICLE (promoter of MAT2A- antisense radiation-induced circulating lncRNA; PARTICL) becomes dramatically instigated within a day after LDR exposure introduced a new gene regulator onto the biological landscape. PARTICLE affords an RNA binding platform for genomic silencers such as DNA methyltransferase 1 and histone tri-methyltransferases to reign in the expression of tumor suppressors such as its neighboring MAT2A in cis as well as WWOX in trans. In silico evidence offers scope to speculate that PARTICLE exploits the abundance of Hoogsten bonds that exist throughout mammalian genomes for triplex formation, presumably a vital feature within this RNA silencer. PARTICLE may provide a buffering riboswitch platform for S-adenosylmethionine. The correlation of PARTICLE triplex formation sites within tumor suppressor genes and their abundance throughout the genome at cancer-related hotspots offers an insight into potential avenues worth exploring in future therapeutic endeavors.
AU  - O'Leary, V.B.
AU  - Ovsepian, S.V.*
AU  - Smida, J.
AU  - Atkinson, M.J.
C1  - 55995
C2  - 46744
CY  - 111 River St, Hoboken 07030-5774, Nj Usa
SP  - 19464-19470
TI  - PARTICLE - The RNA podium for genomic silencers.
JO  - J. Cell. Physiol.
VL  - 234
IS  - 11
PB  - Wiley
PY  - 2019
SN  - 0021-9541
ER  - 

TY  - JOUR
AB  - In the last few years, new approaches and developments in patient-tailored cancer therapies have raised the need to select, more precisely, those patients who will respond to personalized treatments. Therefore, the most efficient way for optimal therapy and patient selection is to provide a tumour-specific protein network portrait prior to treatment. The aim of our study was to monitor protein networks in formalin-fixed and paraffin-embedded (FFPE) breast cancer tissues, with special emphasis on epidermal growth factor receptor 2 (HER2)-mediated signalling pathways, to identify and validate new disease markers. For this purpose we used a recently developed technology to extract full-length proteins from FFPE tissues and analysed 23 molecules involved in HER2-related signalling by reverse phase protein microarray (RPPA) in a series of 106 FFPE breast cancer tissue samples. We found a significant correlation of HER2 with human epidermal growth factor receptor 3 (HER3/erbB3), epidermal growth factor receptor 1 (EGFR/HER1/erbB1) and urokinase plasminogen receptor (uPAR) in routinely used FFPE breast cancer tissues. Thus, targeting HER2, EGFR, HER3 and uPAR together may offer a more efficient treatment option for patients with breast cancer.
AU  - Berg, D.*
AU  - Wolff, C.*
AU  - Malinowsky, K.*
AU  - Tran, K.*
AU  - Walch, A.K.
AU  - Bronger, H.*
AU  - Schuster, T.*
AU  - Höfler, H.*
AU  - Becker, K.-F.*
C1  - 7237
C2  - 29582
SP  - 204-212
TI  - Profiling signalling pathways in formalin-fixed and paraffin-embedded breast cancer tissues reveals cross-talk between EGFR, HER2, HER3 and uPAR.
JO  - J. Cell. Physiol.
VL  - 227
IS  - 1
PB  - Wiley-Blackwell
PY  - 2012
SN  - 0021-9541
ER  - 

TY  - JOUR
AB  - The nuclear isoform of the selenoprotein Phospholipid Hydroperoxide Glutathione Peroxidase (nGPx4) is expressed in haploid male germ cells, contains several cysteines and is able to oxidize protein thiols, besides glutathione. In this study we have investigated the subnuclear localization of this isoform in isolated mouse male germ cells at different steps of maturation. Immunoblotting and confocal microscopy analyses of subnuclear fractions showed that nGPx4 is localized to the nuclear matrix together with well known markers of this subnuclear compartment like lamin B and topoisomerase IIβ at all stages of germ cell differentiation. The peculiar nGPx4 distribution was confirmed by both biochemical and morphological analyses of COS-1 cells overexpressing Flag-tagged nGPx4. To test the functional role of nGPx4 in the process of chromatin assembly, sperm isolated from the caput and the cauda epididymides of wild-type (WT) and genetically deficient in nGPx4 (nGPx4-KO) mice were analysed in an in vitro chromatin decondensation assay. Results showed that sperm from nGPx4-KO mice were more prone to decondense than those from WT mice at all stages of epididymal maturation, providing conclusive evidence that nGPx4 is required for a correct sperm chromatin compaction. We next addressed the issue of whether the lack of nGPx4 impacts on early events occurring at fertilization. Indeed, in vitro fertilization experiments showed an acceleration of sperm chromatin dispersion in oocytes fertilized by nGpx4-KO sperm compared with control. Overall these data indicate that the absence of nGPx4 leads to sperm nuclear matrix /chromatin instability that may negatively affect the embryo development.
AU  - Puglisi, R.*
AU  - Maccari, I.*
AU  - Pipolo, S.*
AU  - Conrad, M.
AU  - Mangia, F.*
AU  - Boitani, C.*
C1  - 5968
C2  - 28721
SP  - 1420-1427
TI  - The nuclear form of Glutathione Peroxidase 4 is associated with sperm nuclear matrix and is required for proper paternal chromatin decondensation at fertilization.
JO  - J. Cell. Physiol.
VL  - 227
IS  - 4
PB  - Wiley-Blackwell
PY  - 2012
SN  - 0021-9541
ER  - 

TY  - JOUR
AU  - Fuchs, M.*
AU  - Hermannstädter, C.*
AU  - Specht, K.*
AU  - Knyazev, P.*
AU  - Ullrich, A.*
AU  - Rosivatz, E.*
AU  - Busch, R.*
AU  - Hutzler, P.
AU  - Höfler, H.
AU  - Luber, B.*
C1  - 830
C2  - 22830
SP  - 805-813
TI  - Effect of tumor-associated mutant E-cadherin variants with defects in exons 8 or 9 on matrix metalloproteinase 3.
JO  - J. Cell. Physiol.
VL  - 202
PB  - Wiley
PY  - 2005
SN  - 0021-9541
ER  - 

TY  - JOUR
AB  - The development of tetrahydrobiopterin synthesis during lectin stimulation of resting human T lymphocytes (Kerler et al. [1989] FEBS Lett., 250:622-624), the interferon-γ induced neopterin production by human monocytes/macrophages (Huber et al. [1984] J. Exp. Med., 160:310-316), and the control of tetrahydrobiopterin synthesis in activated T cells by the synergistic action of interferon-γ and interleukin 2 (Ziegler et al. [1990] J. Biol. Chem., 265:17026-17030) were previously explained by modulation of the apparent GTP-cyclohydrolase I activation. In this study we demonstrate that increases in GTP-cyclohydrolase I activity which occur after lectin induction and after cytokine treatment correlate with increased steady state mRNA levels specific for this enzyme. The enhancement of interferon-γ induced enzyme activity in primed T cells by interleukin 2 also corresponds to further increases in mRNA expression. The steady state GTP-cyclohydrolase I mRNA levels in primed T cells, however, do not correlate with the steep decline which follows the culmination of enzyme activity 44 hours after treatment. This indicates that the down-regulation of apparent GTP-cyclohydrolase I activity is caused by posttranslational modification of the protein.
AU  - Schott, K.
AU  - Gütlich, M.
AU  - Ziegler, I.
C1  - 40286
C2  - 13614
SP  - 12-16
TI  - Induction of GTP-cyclohydrolase I mRNA expression by lectin activation and interferon-γ treatment in human cells associated with the immune response.
JO  - J. Cell. Physiol.
VL  - 156
IS  - 1
PY  - 1993
SN  - 0021-9541
ER  - 

TY  - JOUR
AB  - The enzymes of tetrahydrobiopterin synthesis have been studied in murine bone marrow, in spleen, in erythrocytes, and in reticulocytes. Mice with chemically induced and with genetically conditioned reticulocytosis as found in the lactate dehydrogenase deficient strain (Ldh-1c/Ldh-1c) were used for analysis of reticulocytic enzyme activities. The activity of the biopterin synthesizing system is highest in bone marrow even though it amounts to only about 10% as compared with liver. The first enzyme of the biosynthetic pathway, GTP-cyclohydrolase, virtually disappears during the final maturation step of reticulocytes. In contrast, the activities of 6-pyruvoyltetrahydropterin synthase and of sepiapterin reductase of erythrocytes are only reduced to about one half of the reticulocyte level. The absence of biopterin in erythrocytes is therefore caused by the loss of the enzyme that initiates the pterin biosynthetic pathway.
AU  - Kerler, F.
AU  - Hültner, L.
AU  - Ziegler, I.
AU  - Katzenmaier, G.
AU  - Bacher, A.
C1  - 18143
C2  - 11003
SP  - 268-271
TI  - Analysis of the Tetrahydrobiopterin Synthesizing System During Maturation of Murine Reticulocytes.
JO  - J. Cell. Physiol.
VL  - 142
IS  - 2
PY  - 1990
SN  - 0021-9541
ER  - 

TY  - JOUR
AB  - The enzymes of tetrahydrobiopterin synthesis have been studied in murine bone marrow, in spleen, in erythrocytes, and in reticulocytes. Mice with chemically induced and with genetically conditioned reticulocytosis as found in the lactate dehydrogenase deficient strain (Ldh-1(c)/Ldh-1(c)) were used for analysis of reticulocytic enzyme activities. The activity of the biopterin synthesizing system is highest in bone marrow even though it amounts to only about 10% as compared with liver. The first enzyme of the biosynthetic pathway, GTP-cyclohydrolase, virtually disappears during the final maturation step of reticulocytes. In contrast, the activities of 6-pyruvoyltetrahydropterin synthase and of sepiapterin reductase of erythrocytes are only reduced to about one half of the reticulocyte level. The absence of biopterin in erythrocytes is therefore caused by the loss of the enzyme that initiates the pterin biosynthetic pathway.
AU  - Kerler, F.
AU  - Hültner, L.
AU  - Ziegler, I.
AU  - Katzenmaier, G.
AU  - Bacher, A.
C1  - 41154
C2  - 36438
SP  - 268-271
TI  - Analysis of the tetrahydrobiopterin synthesizing system during maturation of murine reticulocytes.
JO  - J. Cell. Physiol.
VL  - 142
IS  - 2
PY  - 1990
SN  - 0021-9541
ER  -