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1.
Cell Death Differ ; 23(3): 454-68, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26383973

ABSTRACT

Endoplasmic reticulum (ER) stress, defective autophagy and genomic instability in the central nervous system are often associated with severe developmental defects and neurodegeneration. Here, we reveal the role played by Rint1 in these different biological pathways to ensure normal development of the central nervous system and to prevent neurodegeneration. We found that inactivation of Rint1 in neuroprogenitors led to death at birth. Depletion of Rint1 caused genomic instability due to chromosome fusion in dividing cells. Furthermore, Rint1 deletion in developing brain promotes the disruption of ER and Cis/Trans Golgi homeostasis in neurons, followed by ER-stress increase. Interestingly, Rint1 deficiency was also associated with the inhibition of the autophagosome clearance. Altogether, our findings highlight the crucial roles of Rint1 in vivo in genomic stability maintenance, as well as in prevention of ER stress and autophagy.


Subject(s)
Autophagy , Brain/metabolism , Endoplasmic Reticulum Stress , Genomic Instability , Tumor Suppressor Proteins/genetics , Vesicular Transport Proteins/genetics , Animals , Apoptosis , Brain/cytology , Cells, Cultured , Mice, 129 Strain , Mice, Transgenic , Mitosis , Neural Stem Cells/physiology , Primary Cell Culture , Purkinje Cells/physiology , Tumor Suppressor Proteins/metabolism , Vesicular Transport Proteins/metabolism
2.
Reprod Biol Endocrinol ; 4: 35, 2006 Jul 07.
Article in English | MEDLINE | ID: mdl-16827936

ABSTRACT

FSH, which binds to specific receptors on granulosa cells in mammals, plays a key role in folliculogenesis. Its biological activity involves stimulation of intercellular communication and upregulation of steroidogenesis, but the entire spectrum of the genes regulated by FSH has yet to be fully characterized. In order to find new regulated transcripts, however rare, we have used a Suppression Subtractive Hybridization approach (SSH) on pig granulosa cells in primary culture treated or not with FSH. Two SSH libraries were generated and 76 clones were sequenced after selection by differential screening. Sixty four different sequences were identified, including 3 novel sequences. Experiments demonstrated the presence of 25 regulated transcripts.A gene ontology analysis of these 25 genes revealed (1) catalytic; (2) transport; (3) signal transducer; (4) binding; (5) anti-oxidant and (6) structural activities. These findings may deepen our understanding of FSH's effects. Particularly, they suggest that FSH is involved in the modulation of peroxidase activity and remodelling of chromatin.


Subject(s)
Follicle Stimulating Hormone/pharmacology , Gene Expression Profiling/methods , Granulosa Cells/drug effects , Subtraction Technique , Animals , Blotting, Northern , Cells, Cultured/drug effects , Cells, Cultured/metabolism , Chromosome Mapping , DNA, Complementary/genetics , Female , Gene Expression Regulation , Gene Library , Granulosa Cells/metabolism , Nucleic Acid Hybridization , Receptors, FSH/drug effects , Receptors, FSH/physiology , Reverse Transcriptase Polymerase Chain Reaction , Sequence Analysis, DNA , Sus scrofa , Transcription, Genetic
3.
Comp Biochem Physiol B Biochem Mol Biol ; 128(2): 275-83, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11207441

ABSTRACT

The low dietary starch utilisation by rainbow trout (Oncorhynchus mykiss) may be attributed to a dysfunction of the nutritional regulation of the hepatic glucose/glucose-6-phosphate cycle. The present study was initiated to analyse the regulation of activity and gene expression of hepatic glucokinase (GK) and glucose-6-phosphatase (G6Pase) by dietary carbohydrates in this species. We found that even a single meal containing 24% of glucose is sufficient to induce the GK expression (mRNA and activity) as in mammals. In contrast, although the inhibitory effect of dietary glucose on G6Pase expression is observed at the molecular level, the G6Pase activity is not significantly inhibited by dietary glucose. Thus, in contrast to the gluconeogenic G6Pase enzyme, a rapid adaptation of the hepatic glycolytic GK enzyme to dietary glucose seems effective in rainbow trout. These results suggest that in carnivorous rainbow trout, the liver is capable to strongly regulate the utilisation of glucose but not the synthesis of glucose.


Subject(s)
Glucokinase/biosynthesis , Glucose-6-Phosphatase/biosynthesis , Glucose/pharmacology , Liver/enzymology , Animals , Blotting, Northern , Gene Expression Regulation, Enzymologic , Oncorhynchus mykiss , RNA/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Time Factors
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