scholarly journals Hypothyroidism alters the expression of Bcl-2 family genes to induce enhanced apoptosis in the developing cerebellum

2003 ◽  
Vol 176 (1) ◽  
pp. 39-46 ◽  
Author(s):  
R Singh ◽  
G Upadhyay ◽  
S Kumar ◽  
A Kapoor ◽  
A Kumar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Fragmentation ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cell Loss ◽  
Apoptotic Gene ◽  
Euthyroid State ◽  
Family Gene ◽  
Apoptotic Genes ◽  
High Level

Thyroid hormone (TH) deficiency results in delayed proliferation and migration of cerebellar granule cells. Although extensive cell loss during the development of the cerebellum under hypothyroid conditions is known, its nature and its mechanism are poorly understood. Bcl-2 family gene expression is known to determine the fate of cells to undergo apoptosis. We evaluated the effect of hypothyroidism on Bcl-2 family gene expression in the developing rat cerebellum. Electrophoresis and Western blotting were used to analyze DNA fragmentation and expression of DNA fragmentation factor (DFF-45), Bcl-2, Bcl-xL and Bax genes respectively. In the hypothyroid condition, extensive DNA fragmentation and enhanced cleavage of DFF-45 were seen throughout development (postnatal day 0 to day 24) and adulthood whereas they were absent in the euthyroid state. The anti-apoptotic genes Bcl-2 and Bcl-xL were down-regulated and the pro-apoptotic gene Bax was expressed at higher levels compared with the euthyroid state. These results suggest that normal levels of TH prevent cerebellar apoptosis to a large extent, whereas hypothyroidism not only increases the extent but also the duration of apoptosis by down-regulating the anti-apoptotic genes and maintaining a high level of the pro-apoptotic gene Bax.

81 Linoleic acid required for reduction of apoptosis through nuclear transcription factor-kappa B during pig embryo development

2020 ◽  
Vol 32 (2) ◽  
pp. 167
Author(s):  
D. Lee ◽  
K. Choi ◽  
J. Oh ◽  
S. Kim ◽  
M. Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fatty Acids ◽  
Transcription Factor ◽  
Linoleic Acid ◽  
Embryo Development ◽  
Mrna Level ◽  
Metabolic Energy ◽  
Apoptotic Gene ◽  
Nuclear Transcription Factor ◽  
Apoptotic Genes

Recent studies suggest that endogenous and exogenous free fatty acids play various important roles in mammalian oocyte and pre-implantation embryo development. Among fatty acids, linoleic acid (LA) has been reported to affect the apoptosis pathway via nuclear transcription factor-kappa B (NF-κB). The transcription factor NF-κB is a key modulator of apoptosis in a variety of cell types, but to date, this specific function of NF-κB has not been demonstrated in porcine pre-implantation embryos. To examine the effect of linoleic acid on invitro-produced parthenogenetic pig embryos, we treated LA by concentration (0, 10, 25, 50, and 100 µM) to identify developmental rate, NF-κB expression, and mRNA level of apoptotic-related genes. In addition, the mechanism was confirmed by examining the protein and mRNA expression of NF-kb and c-jun by immunostaining and quantitative PCR at the blastocyst stage. Linoleic acid had a positive effect on embryo development without toxicity at a certain concentration (25 µM), but toxicity was confirmed at higher (50-100μM) concentrations. Furthermore, it was confirmed that the concentration of NF-κB increased as the treatment concentration of LA increased, which was found to increase even at the concentration at which embryo development decreased. Previous studies have shown that the NF-κB pathway is involved in regulating anti- and pro-apoptotic gene expression. We also investigated the effects of LA on anti- (Bcl-xL, Mcl-1) and pro- (BAX1, TP53, Caspase3) apoptotic genes and NF-κB activation-related genes (RelA, JNK1, JNK2, IL-6) in porcine embryos. We have found that down-regulation of pro-apoptotic gene expression occurs in the LA-treated group. It was also found that Bcl-xL, one of the anti-apoptotic genes, was not affected by LA, which appears to be an effect of IL-6. In contrast, Mcl-1, an anti-apoptotic gene known not to be affected by IL-6, was found to have increased expression mRNA level in LA-treated pig embryos. Furthermore, through double-staining of apoptosis and immunocytochemistry, as the concentration of NF-kB level increases, the nuclear translocation of c-jun, the protein of which was also related with apoptosis, increased gradually depending on the LA concentration. These data could support that porcine embryo can use exogenous LA as a metabolic energy source. The data also demonstrate the important role of NF-kB in porcine early embryo development. Support was provided by the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through the Development of High Value-Added Food Technology program funded by the Ministry of Agriculture, Food and Rural Affairs (MAFRA, 118042-03-1-HD020).

Cannabinoid agonist WIN55,212-2 induces apoptosis in cerebellar granule cells via activation of the CB1 receptor and downregulation of bcl-xL gene expression

2006 ◽  
Vol 83 (6) ◽  
pp. 1058-1065 ◽  
Author(s):  
Giacomo Pozzoli ◽  
Giuseppe Tringali ◽  
Mauro Vairano ◽  
Monia D'Amico ◽  
Pierluigi Navarra ◽  
...  
Keyword(s):  
Gene Expression ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cb1 Receptor ◽  
Cerebellar Granule ◽  
Cannabinoid Agonist

scholarly journals The Expression of the PDZ Protein MALS-1/Velis Is Regulated by Calcium and Calcineurin in Cerebellar Granule Cells

2002 ◽  
Vol 277 (51) ◽  
pp. 49585-49590 ◽  
Author(s):  
Bastiano Sanna ◽  
Dana Kramer ◽  
Armando A. Genazzani
Keyword(s):  
Gene Expression ◽  
Neuronal Development ◽  
Granule Cells ◽  
De Novo ◽  
Cerebellar Granule Cells ◽  
Transcriptional Level ◽  
Synaptic Density ◽  
Cerebellar Granule ◽  
Activity Dependent ◽  
Post Synaptic Density

Activity-dependent gene expression is thought to be important in shaping neuronal development and in modifying the protein content of neurons. Ca2+entry into neurons appears to be one of the key effectors of activity-dependent gene expression. Among the possible downstream targets of calcium, the protein phosphatase calcineurin represents a prime candidate. We hereby report that in cultured cerebellar granule cells the activation of the Ca2+/calcineurin pathway via either voltage- or ligand- operated Ca2+channels regulates MALS-1 and MALS-2 expression at the transcriptional level. These proteins are integral parts of the post-synaptic density and are also involved in receptor trafficking. MALS regulation is not at the level of mRNA stability and does not requirede novoprotein synthesis, thereby suggesting a direct pathway. These data suggest that Ca2+entry by means of calcineurin is capable of controlling the structure of the post-synaptic density by controlling the expression of key components at the transcriptional level.

98 Gene expression of transcription factors in apoptotic cerebellar granule cells

1996 ◽  
Vol 14 ◽  
pp. 74-74
Author(s):  
D.F. Condorelli ◽  
A. Copani ◽  
A. Calogero ◽  
P. Dell'Albani ◽  
F. Nicoletti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factors ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cerebellar Granule

The absence of pleiotrophin modulates gene expression in the hippocampus in vivo and in cerebellar granule cells in vitro

2016 ◽  
Vol 75 ◽  
pp. 113-121 ◽  
Author(s):  
Celia González-Castillo ◽  
Daniel Ortuño-Sahagún ◽  
Carolina Guzmán-Brambila ◽  
Ana Laura Márquez-Aguirre ◽  
Rita Raisman-Vozari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Granule Cells ◽  
Cerebellar Granule Cells ◽  
Cerebellar Granule
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