Abnormal lipid metabolism induced apoptosis of spermatogenic cells by increasing testicular HSP60 protein expression

Andrologia ◽  
2020 ◽  
Vol 52 (11) ◽  
Author(s):  
Lixian Cheng ◽  
Xue Yi ◽  
Ying Shi ◽  
Shuwei Yu ◽  
Liyuan Zhang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Protein Expression ◽  
Spermatogenic Cells ◽  
Induced Apoptosis ◽  
Abnormal Lipid Metabolism ◽  
Hsp60 Protein

ANP32A Regulates Histone 3 Acetylation and Promotes Leukemogenesis in AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3917-3917
Author(s):  
Xuejing Yang ◽  
Xueqin Sun ◽  
Bin Lu ◽  
Qianfei Wang ◽  
Zan Huang
Keyword(s):  
Gene Expression ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Lipid Metabolism ◽  
Protein Expression ◽  
K562 Cells ◽  
Metabolic Process ◽  
Histone 3 ◽  
Induced Apoptosis

Abstract Leukemia initiation and progression not only depend on genetic alterations but also on abnormal epigenetic changes that cause disorder of gene expression. Acidic leucine-rich nuclear phosphoprotein-32A (ANP32A) binds directly to histone tails, preferentially to unmodified histone H3 tails (Schneider et al., 2004; Seo et al., 2002). Although ANP32A inhibits histone acetyltransferase activity in vitro (Seo et al., 2002), loss of ANP32A leads to decreased histone 3 acetylation (acetyl-H3) levels on interferon-stimulated genes in human cervical carcinoma HeLa S3 cells (Kadota et al., 2011). Aberrant ANP32A expression has been observed in many solid tumors, which involves in diverse processes depending on the cell context (Brody et al., 2004; Hoffarth et al., 2008), yet mechanisms are still unknown. Furthermore, there has as yet been no specific investigation into the role of ANP32A in acute myeloid leukemia (AML). We found that ANP32A expression was upregulated at both mRNA and protein levels in patients with AML. In AML primary cells from patients, ANP32A KD decreased cell proliferation and colony formation ability. In addition, ANP32A KD induced apoptosis and cell cycle arrest at G1 phase accompanied with the downregulated protein expression of survival or cell cycle progress genes BCL2, CDK4, CCND1 and the upregulated protein expression of pro-apoptosis genes BAK, BAD, cleaved caspase 3. These findings were also verified in various subtypes of AML cell lines and Mll-Af9 pre-leukemic cells. Thus, ANP32A is essential for cell growth via the promotion of cell-cycle progression and inhibition of apoptosis in AML. Given that ANP32A associates with histone acetylation modification, we analyzed the effect of ANP32A depletion on acetyl-H3 and histone 4 acetylation (acetyl-H4). Western blot analysis showed that ANP32A KD caused global decrease of acetyl-H3, but no effect on the global level of acetyl-H4. To investigate the mechanism of ANP32A in AML, ChIP-seq and gene expression microarray experiments were performed to determine acetyl-H3 enrichment and transcriptome profiles, respectively, in ANP32A KD and control K562 cells. We found a positive correlation between changes in gene expression and changes in acetyl-H3 (r=0.16, p<10-4), especially for differential expression genes (DEGs; r=0.40, p<10-4). Moreover, we also found genes with decreased acetyl-H3 enrichment displayed lower expression levels compared with genes with increased acetyl-H3 enrichment (p<10-3). Thus, ANP32A alters acetyl-H3 modification in association with changes in gene expression. Gene set enrichment analysis (GSEA) revealed that ANP32A KD significantly decreased the acetyl-H3 enrichment levels at genes of lipid metabolism signatures (e.g. lipid metabolic process, cholesterol homeostasis). Transcriptome profile analysis using GSEA showed that gene expression levels of lipid metabolic process signature were also reduced after ANP32A KD. We further identified 4 genes (APOC1, CNKSR3, H19, PCSK9) which had significantly lower levels of mRNA expression (p<10-2, FDR<10-2, FC>1.5) and decreased levels of acetyl-H3 enrichment (p<10-2, FDR<10-2, FC>1.5) in ANP32A KD cells. Apolipoprotein CI(APOC1) was the most significantly downregulated gene among these 4 genes, with decreased acetyl-H3 on its promoter. To explore whether lipid metabolism as a downstream effector of ANP32A contributes to ANP32A function in AML, re-introduction of APOC1 was performed in ANP32A KD THP1 or K562 cells. Re-introduction of APOC1 significantly rescued the inhibition of cell growth in ANP32A KD AML cells, also upregulated protein expression of BCL2, CDK4 and CCND1, showing that ANP32A functions in AML partially depending on APOC1. Importantly, APOC1 depletion decreased cell proliferation of AML cells in vitro, consistent with the point of view that complex lipid alterations contribute to endoplasmic reticulum stress-induced apoptosis in cancer cells (Beloribi-Djefaflia et al., 2016; Iurlaro et al., 2016). Overall, our data suggest ANP32A as a novel regulator of leukemogenesis in AML. ANP32A may involve in the regulation of genome-wide histone 3 acetylation that alters the expression of multiple genes, including lipid metabolism related gene APOC1. Thus, ANP32A is a promising drug target for AML therapy. Disclosures No relevant conflicts of interest to declare.

scholarly journals Mirtronic miR-4646-5p promotes gastric cancer metastasis by regulating ABHD16A and metabolite lysophosphatidylserines

2021 ◽  
Author(s):  
Liping Yang ◽  
Yixuan Hou ◽  
Yan-e Du ◽  
Qiao Li ◽  
Fanlin Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lipid Metabolism ◽  
Gastric Cancer Cell ◽  
Cancer Metastasis ◽  
Host Gene ◽  
Diagnostic Biomarker ◽  
Invasion And Metastasis ◽  
Gastric Cancer Cells ◽  
Tumor Progress ◽  
Abnormal Lipid Metabolism

AbstractThe aberrant classical miRNAs are considered to play significant roles in tumor progression. However, it remains unclear for nonclassical miRNAs, a set of Drosha-independent miRNAs in the process of various biology. Here, we reveal that a nonclassical miR-4646-5p plays a pivotal role in gastric cancer (GC) metastasis. MiR-4646-5p, one of Drosha-independent mirtronic miRNA, is aberrant up-regulated in Drosha-low expressed GC and Drosha-knockdown gastric cancer cells. Mirtronic miR-4646-5p is a specific transcription splicing product of intron 3 of the host gene Abhd16a with the aid of SRSF2. The enhanced miR-4646-5p can stabilize HIF1A by targeting PHD3 to positive feedback regulate Abhd16a and miR-4646-5p itself expressions. ABHD16A, as an emerging phosphatidylserine-specific lipase, involves in lipid metabolism leading to lysophosphatidylserines (lyso-PSs) accumulation, which stimulates RhoA and downstream LIMK/cofilin cascade activity through GPR34/Gi subunit, thus causes metastasis of gastric cancer. In addition, miR-4646-5p/PHD3/HIF1A signaling can also up-regulate RhoA expression and synergistically promote gastric cancer cell invasion and metastasis. Our study provides new insights of nonclassical mirtronic miRNA on tumor progress and may serve as a new diagnostic biomarker for gastric cancer. MiR-4646-5p and its host gene Abhd16a mediated abnormal lipid metabolism may be a new target for clinical treatment of gastric cancer.

Apigenin protects mice against 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestasis

2021 ◽  
Vol 12 (5) ◽  
pp. 2323-2334
Author(s):  
Shihong Zheng ◽  
Peichang Cao ◽  
Zequn Yin ◽  
Xuerui Wang ◽  
Yuanli Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Liver Fibrosis ◽  
Liver Damage ◽  
Liver Diseases ◽  
Potential Drug ◽  
Abnormal Lipid Metabolism ◽  
And Oxidative Stress

Apigenin prevented the DDC-induced abnormal lipid metabolism, liver damage and liver fibrosis by reducing inflammation and oxidative stress. Apigenin might be a potential drug for the treatment of cholestatic liver diseases.

scholarly journals Overexpression of CRABP2 inhibits dexamethasone-induced apoptosis in human osteoblast cells

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Haiping Zhang ◽  
Ziliang Yu ◽  
Farui Sun ◽  
Jin Jin
Keyword(s):  
Protein Expression ◽  
Underlying Mechanism ◽  
R Package ◽  
Treated Group ◽  
Gene Expression Omnibus ◽  
Human Osteoblast ◽  
Osteoblast Cells ◽  
Gene And Protein Expression ◽  
Osteoblast Apoptosis ◽  
Induced Apoptosis

Abstract Background The purpose of the current study was to explore the role and underlying mechanism of cellular retinoic acid binding protein 2 (CRABP2) in dexamethasone (DEX)-induced apoptosis in human osteoblast cells. Methods GSE10311 was downloaded from the Gene Expression Omnibus (GEO) database to identify the differentially expressed genes (DEGs) by the limma/R package. Primary human osteoblast was isolated and treated with different concentration of DEX (0, 10-8, 10-7, 10-6, 10-5, and 10-4 mol/L), and cell viability and flow cytometry were used to detect cell proliferation and apoptosis. A CRABP2 overexpression plasmid (oe-CRABP2) was used to overexpress CRABP2, and western blotting was conducted to detect protein expression. Results We found that CRABP2 was downregulated in the DEX-treated group. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that DEGs were associated with PI3K/Akt signaling pathway. DEX downregulated CRABP2 gene and protein expression, inhibited viability, and induced human osteoblast apoptosis. Overexpression of CRABP2 reversed DEX-induced apoptosis in human osteoblast. Moreover, overexpression of CRABP2 delayed the progression of DEX-induced osteonecrosis of the femoral head (ONFH) animal model. Conclusion In conclusion, CRABP2 is effective at inhibiting DEX-induced human osteoblast apoptosis and delayed ONFH progression.

scholarly journals A grape polyphenol extract modulates muscle membrane fatty acid composition and lipid metabolism in high-fat–high-sucrose diet-fed rats

2011 ◽  
Vol 106 (4) ◽  
pp. 491-501 ◽  
Author(s):  
Manar Aoun ◽  
Francoise Michel ◽  
Gilles Fouret ◽  
Audrey Schlernitzauer ◽  
Vincent Ollendorff ◽  
...  
Keyword(s):  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Protein Expression ◽  
Acid Composition ◽  
Phospholipid Fatty Acid ◽  
Phospholipid Fatty Acid Composition ◽  
High Fat ◽  
Gene And Protein Expression ◽  
High Sucrose

Accumulation of muscle TAG content and modification of muscle phospholipid fatty acid pattern may have an impact on lipid metabolism, increasing the risk of developing diabetes. Some polyphenols have been reported to modulate lipid metabolism, in particular those issued from red grapes. The present study was designed to determine whether a grape polyphenol extract (PPE) modulates skeletal muscle TAG content and phospholipid fatty acid composition in high-fat–high-sucrose (HFHS) diet-fed rats. Muscle plasmalemmal and mitochondrial fatty acid transporters, GLUT4 and lipid metabolism pathways were also explored. The PPE decreased muscle TAG content in HFHS/PPE diet-fed rats compared with HFHS diet-fed rats and induced higher proportions of n-3 PUFA in phospholipids. The PPE significantly up-regulated GLUT4 mRNA expression. Gene and protein expression of muscle fatty acid transporter cluster of differentiation 36 (CD36) was increased in HFHS diet-fed rats but returned to control values in HFHS/PPE diet-fed rats. Carnitine palmitoyltransferase 1 protein expression was decreased with the PPE. Mitochondrial β-hydroxyacyl CoA dehydrogenase was increased in HFHS diet-fed rats and returned to control values with PPE supplementation. Lipogenesis, mitochondrial biogenesis and mitochondrial activity were not affected by the PPE. In conclusion, the PPE modulated membrane phospholipid fatty acid composition and decreased muscle TAG content in HFHS diet-fed rats. The PPE lowered CD36 gene and protein expression, probably decreasing fatty acid transport and lipid accumulation within skeletal muscle, and increased muscle GLUT4 expression. These effects of the PPE are in favour of a better insulin sensibility.

Abnormal Lipid Metabolism in Primary Nephrotic Syndrome

1987 ◽  
pp. 33-43
Author(s):  
Gaston Zilleruelo ◽  
S. L. Hsia ◽  
Michael Freundlich ◽  
Carolyn Abitbol ◽  
Milan Novak ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Lipid Metabolism ◽  
Primary Nephrotic Syndrome ◽  
Abnormal Lipid Metabolism

scholarly journals THE EFFECT OF NONI (Morinda citrifolia) EXTRACT TO HEPAR HISTOPATHOLOGY AND TRIGLYCERIDE LEVEL IN RATS (Rattus Norvegicus) INDUCED BY DISLIPIDEMIA

2019 ◽  
Vol 20 (2) ◽  
pp. 76-81
Author(s):  
Jhouharotul Faradisah ◽  
Diah Purwaningsari
Keyword(s):  
Lipid Metabolism ◽  
Triglyceride Level ◽  
Rattus Norvegicus ◽  
Morinda Citrifolia ◽  
Control Group ◽  
High Cholesterol Diet ◽  
Cholesterol Diet ◽  
High Cholesterol ◽  
White Rats ◽  
Abnormal Lipid Metabolism

Dyslipidemia is an abnormal lipid metabolism which may cause fat degeneration on hepatocytes cells and elevated triglyceride serum level. Dyslipidemia can be prevented by the consumption of high antioxidant food. Noni(Morinda citrifolia) contains many antioxidant such as flavanoid, kuersetin, tannin, and saponin, which are able to prohibit the elevation of ROS.This research is aimed to find out the effect of noni(Morinda citrifolia) extract in reducing the number of hepatocyte’s cells with fat degeneration and decreasing the triglyceride level which is elevated due to high cholesterol diet induction.In this study white rats divided randomly into 4 groups, control group (K-), high cholesterol diet induced group (K+), high cholesterol diet induced with 100 mg/Kg BW noni extract group (P1), high cholesterol diet induced with 200 mg/Kg BW noni extract group (P2). The result shows that noni  extract with dose 100 mg/Kg BW and  200 mg/Kg BWcan reduce the number of hepatocytes cells with fat degeneration (p= 0,026 and p=0,027) and decrease the level of triglyceride serum (p=0,036 and p=0,010).The conclusion is noni extract with dose 100 mg/KgBW reduces effectively  the number of hepatocyte’s cells with fat degeneration and decreases the level of triglyceride serum which increase because of high cholesterol diet. 

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