Folic acid rivals methylenetetrahydrofolate reductase (MTHFR) gene-silencing effect on MEPM cell proliferation and apoptosis

2006 ◽  
Vol 292 (1-2) ◽  
pp. 145-154 ◽  
Author(s):  
Wen-lin Xiao ◽  
Min Wu ◽  
Bing Shi
Keyword(s):  
Cell Proliferation ◽  
Folic Acid ◽  
Gene Silencing ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Proliferation And Apoptosis

scholarly journals A Novel Review of Homocysteine and Pregnancy Complications

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Chuce Dai ◽  
Yiming Fei ◽  
Jianming Li ◽  
Yang Shi ◽  
Xiuhua Yang
Keyword(s):  
Folic Acid ◽  
Pregnancy Complications ◽  
Methylenetetrahydrofolate Reductase ◽  
Normal Pregnancy ◽  
Positive Outcome ◽  
Mthfr Gene ◽  
Folate Intake ◽  
Daily Diet ◽  
B12 Deficiency ◽  
Work Done

Homocysteine (Hct) is a substance produced in the metabolism of methionine. It is an essential type of amino acid gained from the daily diet. Methylenetetrahydrofolate reductase (MTHFR) gene mutation is related to elevated total homocysteine (tHct) expressions, in particular, among women with low folate intake. Hyperhomocysteinemia (HHct) is caused by numerous factors, such as genetic defects, lack of folic acid, vitamin B6 and B12 deficiency, hypothyroidism, drugs, aging, and renal dysfunction. Increased Hct in peripheral blood may lead to vascular illnesses, coronary artery dysfunction, atherosclerotic changes, and embolic diseases. Compared to nonpregnant women, the Hct level is lower in normal pregnancies. Recent studies have reported that HHct was associated with numerous pregnancy complications, including recurrent pregnancy loss (RPL), preeclampsia (PE), preterm delivery, placental abruption, fetal growth restriction (FGR), and gestational diabetes mellitus (GDM). Besides, it was discovered that neonatal birth weight and maternal Hct levels were negatively correlated. However, a number of these findings lack consistency. In this review, we summarized the metabolic process of Hct in the human body, the levels of Hct in different stages of normal pregnancy reported in previous studies, and the relationship between Hct and pregnancy complications. The work done is helpful for obstetricians to improve the likelihood of a positive outcome during pregnancy complications. Reducing the Hct level with a high dosage of folic acid supplements during the next pregnancy could be helpful for females who have suffered pregnancy complications due to HHct.

scholarly journals Effects of PKM2 Gene Silencing on the Proliferation and Apoptosis of Colorectal Cancer LS-147T and SW620 Cells

2017 ◽  
Vol 42 (5) ◽  
pp. 1769-1778 ◽  
Author(s):  
Ran Ao ◽  
Lin Guan ◽  
Ying Wang ◽  
Jia-Ni Wang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Gene Silencing ◽  
Cell Counting ◽  
Qrt Pcr ◽  
Empty Plasmid ◽  
Proliferation And Apoptosis ◽  
Mrna And Protein Expression ◽  
Sw620 Cells

Background/Aims: This paper aims to explore the effects of pyruvate kinase (PK) M2 gene silencing on the proliferation and apoptosis of colorectal cancer (CRC) LS-147T and SW620 cells. Methods: CRC LS-147T and SW620 cells highly expressing PKM2 were randomly selected by quantitative real-time polymerase chain reaction (qRT-PCR) and then assigned into the blank (no transfection), PKM2-shRNA (transfection with shRNA) and empty plasmid (transfection with empty plasmid) groups. Immunofluorescence was applied to detect PKM2 protein expression. qRT-PCR and Western blotting were conducted to assess mRNA and protein expression of PKM2, p53 and p21. The cell counting kit-8 (CCK-8) assay was used to assess cell proliferation. Flow cytometry was used to assess the cell cycle and apoptosis rate, and a senescence-associated β-galactosidase staining kit was used to assess cell senescence. Results: PKM2 exhibited high mRNA expression among CRC LS-147T and SW620 cells with remarkable protein expression noted in the cytoplasm and nucleus. The PKM2-shRNA group exhibited reduced PKM2 mRNA and protein expression, whereas p53 and p21 expression was increased compared with the blank and empty plasmid groups. Cell proliferation in PKM2-shRNA cells decreased significantly compared with the blank group and empty plasmid groups. The PKM2-shRNA group exhibited more cells in the G1 phase and fewer cells in the G2/M phase compared with the blank and empty plasmid groups. In addition, the PKM2-shRNA group exhibited significantly increased apoptosis rates and β-galactosidase activity compared with the blank and empty plasmid groups. Conclusion: Our study demonstrates that PKM2 gene silencing suppresses proliferation and promotes apoptosis in LS-147T and SW620 cells.

scholarly journals Folic Acid Exerts Dose-Dependent Biphasic Effects on Cardiac Development of Zebrafish Embryos

2021 ◽  
Author(s):  
Xuhui Han ◽  
Bingqi Wang ◽  
Hongjie Wang ◽  
Yao Zu
Keyword(s):  
Folic Acid ◽  
Methylenetetrahydrofolate Reductase ◽  
Cardiac Development ◽  
Mthfr Gene ◽  
Folate Metabolism ◽  
Marker Genes ◽  
Zebrafish Embryos ◽  
Cardiovascular Development ◽  
Knock Out ◽  
Dose Dependent

Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is significantly associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. And we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid, and mthfr-/- mutant all gave rise to early pericardial edema and cardiac defect at 3 days after fertilization(dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5dpf. The expression levels of cardiac marker genes hand2, gata4 and nppa changed in the abnormality of folate metabolism embryos and mthfr-/- mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. And our results reveal that folic acid has a dose-dependent biphasic effect on early cardiac development.

scholarly journals Multiple gene silencing in STAT pathway in K562 cells

2019 ◽  
Vol 4 ◽  
pp. 13-20
Author(s):  
Vinod Rajendran ◽  
Sudha S. Deo
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Gene Silencing ◽  
Cell Line ◽  
Quantitative Polymerase Chain Reaction ◽  
K562 Cells ◽  
Inhibition Of Proliferation ◽  
Multiple Gene ◽  
Proliferation And Apoptosis ◽  
Multiple Gene Silencing

Context: Chronic myeloid leukemia (CML) is characterized by the presence of a fusion oncoprotein BCR-ABL. This mutation imparts a constitutive phosphorylation activity of tyrosine residues in the cellular proteins. One of the targets of BCR-ABL is the STAT5 protein, which when phosphorylated induces gene expression of antiapoptotic proteins such as BCL-XL. The STAT pathway has been targeted in the past by disrupting any one protein only. A multiple gene silencing has never been done in this pathway. Aim: The aim of this study was to compare the effects of downregulation of BCR-ABL, STAT5A, STAT5B, and BCL-XL, individually and simultaneously, in human CML cell line (K562 cells) through RNA interference (RNAi). Further, gene expression, inhibition of proliferation, and apoptosis induction were assessed in K562 cells. Materials and Methods: K562 cells were transfected with various combinations of small iRNA (siRNA) and the expressions of aforesaid genes were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. K562 cell proliferation and apoptosis were analyzed using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and flow cytometry, respectively. The results were compared through one-way analysis of variance. Results: qPCR and western blotting results post-siRNA transfection confirmed the targeted gene suppression and protein reduction in K562 cells. The cell proliferation assay and apoptosis assay revealed that simultaneous gene silencing of BCR-ABL, STAT5A, STAT5B, and BCL-XL had the highest killing effect on K562 cells as compared to knocking down these genes individually or in any other combinations. Conclusions: This was the first time it was shown that multiple gene silencing in STAT pathway in CML cell line K562 was better as compared to individual gene silencing.

scholarly journals In vivo and in vitro effects of hyperplasia suppressor gene on the proliferation and apoptosis of lung adenocarcinoma A549 cells

2018 ◽  
Vol 38 (5) ◽  
Author(s):  
Zhen-Qing Sun ◽  
Gang Chen ◽  
Qiang Guo ◽  
He-Fei Li ◽  
Zhou Wang
Keyword(s):  
Cell Proliferation ◽  
Lung Adenocarcinoma ◽  
Gene Silencing ◽  
Nude Mice ◽  
A549 Cell ◽  
A549 Cells ◽  
Suppressor Gene ◽  
Proliferation And Apoptosis ◽  
Lung Adenocarcinoma A549

Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC). Hyperplasia suppressor gene (HSG) has been reported to inhibit cell proliferation, migration, and remodeling in cardiovascular diseases. However, there lacks systematic researches on the effect of HSG on the apoptosis and proliferation of lung adenocarcinoma A549 cells and data of in vivo experiments. The present study aims to investigate the effects of HSG gene silencing on proliferation and apoptosis of lung adenocarcinoma A549 cells. The human lung adenocarcinoma A549 cell was selected to construct adenovirus vector. Reverse transcription-quantitative PCR (RT-qPCR) and Western blot analysis were conducted to detect expressions of HSG and apoptosis related-proteins. Cell Counting Kit (CCK)-8 assay was performed to assess A549 cell proliferation and flow cytometry to analyze cell cycle and apoptosis rate. The BALB/C nude mice were collected to establish xenograft model. Silenced HSG showed decreased mRNA and protein expressions of HSG, and elevated A549 cell survival rates at the time point of 24, 48, and 72 h. The ratio of cells at G0/G1 phase and apoptosis rate decreased and the ratio of cells at S- and G2/M phases increased following the silencing of HSG. There were decreases of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Caspase-3, and Caspase-8 expressions but increases in Bcl-2 induced by silenced HSG. As for the xenograft in nude mice, tumor volume increased, and apoptosis index (AI) decreased after HSG silencing. These results indicate that HSG gene silencing may promote the proliferation of A549 cells and inhibit the apoptosis. HSG may be a promising target for the treatment of lung adenocarcinoma.

Schizophrenia and folate pharmacogenetics: Review of the literature regarding folic acid and its pharmacogenetically regulated metabolism in relation to schizophrenia treatments

2012 ◽  
Vol 1 (9) ◽  
pp. 225-229 ◽  
Author(s):  
Andrew Wechter ◽  
Kristen N. Gardner ◽  
Tyler B. Grove ◽  
Vicki L. Ellingrod
Keyword(s):  
Metabolic Syndrome ◽  
Folic Acid ◽  
Methylenetetrahydrofolate Reductase ◽  
Mthfr Gene ◽  
Gene Variants ◽  
Cognitive Symptoms ◽  
Review Of The Literature ◽  
Dietary Folate ◽  
The Relationship

Folic acid and its metabolism and utilization has become of increasing importance within the field of schizophrenia. Methylenetetrahydrofolate reductase (MTHFR) is the enzyme responsible for the formation of methyltetrahydrofolate (5-methyl THF) from dietary folate. Multiple studies have demonstrated relationships between MTHFR gene variants and schizophrenia. This review discusses these studies, and their findings regarding the relationship between different variants of the MTHFR gene and risk of antipsychotic-related metabolic syndrome, and the relationship between the pharmacogenetics of folate and the negative/cognitive symptoms of schizophrenia.

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