دورية أكاديمية
أعرض في EDS

Increased Levels of cAMP by the Calcium-Dependent Activation of Soluble Adenylyl Cyclase in Parkin -Mutant Fibroblasts.

التفاصيل البيبلوغرافية
العنوان: Increased Levels of cAMP by the Calcium-Dependent Activation of Soluble Adenylyl Cyclase in Parkin -Mutant Fibroblasts.
المؤلفون: Tanzarella P; Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari 'Aldo Moro', 70124 Bari, Italy. tanzarellapaola87@gmail.com., Ferretta A; Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari 'Aldo Moro', 70124 Bari, Italy. anna.ferretta@uniba.it., Barile SN; Department of Biosciences, Biotechnologies and Biopharmaceutics, University of 'Bari Aldo Moro', 70124 Bari, Italy. simona.barile@uniba.it., Ancona M; Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari 'Aldo Moro', 70124 Bari, Italy. mariellaa83@gmail.com., De Rasmo D; Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, Italian National Research Council (CNR), 70126 Bari, Italy. d.derasmo@ibiom.cnr.it., Signorile A; Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari 'Aldo Moro', 70124 Bari, Italy. anna.signorile@uniba.it., Papa S; Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari 'Aldo Moro', 70124 Bari, Italy. sergio.papa@uniba.it.; Stazione Zoologica Anton Dohrn, 80121 Napoli, Italy. sergio.papa@uniba.it., Capitanio N; Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy. nazzareno.capitanio@unifg.it., Pacelli C; Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy. consiglia.pacelli@unifg.it., Cocco T; Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari 'Aldo Moro', 70124 Bari, Italy. tizianamaria.cocco@uniba.it.
المصدر: Cells [Cells] 2019 Mar 15; Vol. 8 (3). Date of Electronic Publication: 2019 Mar 15.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101600052 Publication Model: Electronic Cited Medium: Print ISSN: 2073-4409 (Print) Linking ISSN: 20734409 NLM ISO Abbreviation: Cells Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI
مواضيع طبية MeSH: Adenylyl Cyclases/*genetics , Calcium/*pharmacology , Cyclic AMP/*metabolism , Fibroblasts/*metabolism , Mutation/*genetics , Ubiquitin-Protein Ligases/*genetics, Adenylyl Cyclases/metabolism ; Cell Membrane/drug effects ; Cell Membrane/metabolism ; Cyclic AMP Response Element-Binding Protein/metabolism ; Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism ; Dantrolene/pharmacology ; Endoplasmic Reticulum/metabolism ; Enzyme Activation/drug effects ; Fibroblasts/drug effects ; Humans ; Mitochondria/drug effects ; Mitochondria/metabolism ; Models, Biological ; Phosphorylation/drug effects ; Solubility ; Transcription, Genetic/drug effects ; Ubiquitin-Protein Ligases/metabolism
مستخلص: Almost half of autosomal recessive early-onset parkinsonism has been associated with mutations in PARK2 , coding for parkin, which plays an important role in mitochondria function and calcium homeostasis. Cyclic adenosine monophosphate (cAMP) is a major second messenger regulating mitochondrial metabolism, and it is strictly interlocked with calcium homeostasis. Parkin -mutant (Pt) fibroblasts, exhibiting defective mitochondrial respiratory/OxPhos activity, showed a significant higher value of basal intracellular level of cAMP, as compared with normal fibroblasts (CTRL). Specific pharmacological inhibition/activation of members of the adenylyl cyclase- and of the phosphodiesterase-families, respectively, as well as quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis, indicate that the higher level of cAMP observed in Pt fibroblasts can contribute to a higher level of activity/expression by soluble adenylyl cyclase (sAC) and to low activity/expression of the phosphodiesterase isoform 4 (PDE4). As Ca 2+ regulates sAC, we performed quantitative calcium-fluorimetric analysis, showing a higher level of Ca 2+ in the both cytosol and mitochondria of Pt fibroblasts as compared with CTRL. Most notably, inhibition of the mitochondrial Ca 2+ uniporter decreased, specifically the cAMP level in PD fibroblasts. All together, these findings support the occurrence of an altered mitochondrial Ca 2+ -mediated cAMP homeostasis in fibroblasts with the parkin mutation.
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فهرسة مساهمة: Keywords: cAMP; calcium; mitochondria; parkin
المشرفين على المادة: 0 (Cyclic AMP Response Element-Binding Protein)
E0399OZS9N (Cyclic AMP)
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
EC 2.3.2.27 (parkin protein)
EC 3.1.4.17 (Cyclic Nucleotide Phosphodiesterases, Type 4)
EC 4.6.1.1 (Adenylyl Cyclases)
F64QU97QCR (Dantrolene)
SY7Q814VUP (Calcium)
تواريخ الأحداث: Date Created: 20190317 Date Completed: 20191203 Latest Revision: 20200309
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6468892
DOI: 10.3390/cells8030250
PMID: 30875974
قاعدة البيانات: MEDLINE
الوصف
تدمد:2073-4409
DOI:10.3390/cells8030250