scholarly journals SOD1 Gene Silencing Promotes Apoptosis and Suppresses Proliferation of Heat-Stressed Bovine Granulosa Cells via Induction of Oxidative Stress

2021 ◽  
Vol 8 (12) ◽  
pp. 326
Author(s):  
Adnan Khan ◽  
Muhammad Zahoor Khan ◽  
Jinhuan Dou ◽  
Huitao Xu ◽  
Lei Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Oxidative Damage ◽  
Granulosa Cells ◽  
Sod1 Gene ◽  
Hormone Synthesis ◽  
Ros Accumulation ◽  
Proliferation And Apoptosis ◽  
Cattle Reproduction ◽  
The Impact

Heat stress (HS) compromises dairy cattle reproduction by altering the follicular dynamics, oocyte maturation, and normal physiological function of ovarian granulosa cells (GCs), eventually resulting in oxidative damage and cell apoptosis. To protect the cells from oxidative damage, the Superoxide dismutase-1 (SOD1) degraded the hydrogen peroxide (H2O2) to oxygen (O2) and water. The objective of the current study was to investigate the impact of SOD1 silencing on intracellular ROS accumulation, cell viability, MMP, hormone synthesis (P4, E2), cell proliferation, and apoptosis in GCs under HS. The mechanistic role of SOD1 regulation in the heat-stressed GCs was explored. SOD1 gene was successfully silenced in GCs and confirmed at both transcriptional and translational levels. We found that silencing of SOD1 using siRNA under HS aggravated intracellular accumulation of reactive oxygen species, apoptosis, disrupted the mitochondrial membrane potential (MMP), altered transition of the cell cycle, and impaired synthesis of progesterone (P4) and estrogen (E2) in GCs. The associative apoptotic, steroidogenic, and cell cycle genes (BAX, Caspase-3, STAR, Cyp11A1, HSP70, PCNA, and CyclinB1) were used to confirm the results. These results identify a novel role of SOD1 in the modulation of bovine ovarian GC apoptosis, which provides a target for improving the fertility of heat-stressed dairy cows in summer.

scholarly journals Modulation of Cathepsin S (CTSS) Regulates the Secretion of Progesterone and Estradiol, Proliferation, and Apoptosis of Ovarian Granulosa Cells in Rabbits

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1770
Author(s):  
Guohua Song ◽  
Yixuan Jiang ◽  
Yaling Wang ◽  
Mingkun Song ◽  
Xuanmin Niu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Hormone Secretion ◽  
Vital Role ◽  
Regulatory Function ◽  
Cathepsin S ◽  
Related Gene ◽  
Ovarian Granulosa Cells ◽  
Proliferation And Apoptosis

Cathepsin S (CTSS) is a member of cysteine protease family. Although many studies have demonstrated the vital role of CTSS in many physiological and pathological processes including tumor growth, angiogenesis and metastasis, the function of CTSS in the development of rabbit granulosa cells (GCS) remains unknown. To address this question, we isolated rabbit GCS and explored the regulatory function of the CTSS gene in cell proliferation and apoptosis. CTSS overexpression significantly promoted the secretion of progesterone (P4) and estrogen (E2) by increasing the expression of STAR and CYP19A1 (p < 0.05). We also found that overexpression of CTSS increased GCS proliferation by up-regulating the expression of proliferation related gene (PCNA) and anti-apoptotic gene (BCL2). Cell apoptosis was markedly decreased by CTSS activation (p < 0.05). In contrast, CTSS knockdown significantly decreased the secretion of P4 and E2 and the proliferation of rabbit GCS, while increasing the apoptosis of rabbit GCS. Taken together, our results highlight the important role of CTSS in regulating hormone secretion, cell proliferation, and apoptosis in rabbit GCS. These results might provide a basis for better understanding the molecular mechanism of rabbit reproduction.

scholarly journals Transcription factor FOXL2 protects granulosa cells from stress and delays cell cycle: role of its regulation by the SIRT1 deacetylase

2011 ◽  
Vol 20 (9) ◽  
pp. 1673-1686 ◽  
Author(s):  
Bérénice A. Benayoun ◽  
Adrien B. Georges ◽  
David L'Hôte ◽  
Noora Andersson ◽  
Aurélie Dipietromaria ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Transcription Factor ◽  
Granulosa Cells

scholarly journals Advances and challenges in cancer treatment and nutraceutical prevention: the possible role of dietary phenols in BRCA regulation

2021 ◽  
Author(s):  
Haroon Khan ◽  
Fabiana Labanca ◽  
Hammad Ullah ◽  
Yaseen Hussain ◽  
Nikolay T. Tzvetkov ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Natural Products ◽  
Cancer Treatment ◽  
Clinical Aspects ◽  
Anti Cancer ◽  
Brca 1 ◽  
Brca 2 ◽  
The Impact ◽  
Cancer Activity

AbstractOver the years, the attention towards the role of phytochemicals in dietary natural products in reducing the risk of developing cancer is rising. Cancer is the second primary cause of mortality worldwide. The current therapeutic options for cancer treatment are surgical excision, immunotherapy, chemotherapy, and radiotherapy. Unfortunately, in case of metastases or chemoresistance, the treatment options become very limited. Despite the advances in medical and pharmaceutical sciences, the impact of available treatments on survival is not satisfactory. Recently, natural products are a great deal of interest as potential anti-cancer agents. Among them, phenolic compounds have gained a great deal of interest, thanks to their anti-cancer activity. The present review focuses on the suppression of cancer by targeting BRCA gene expression using dietary polyphenols, as well as the clinical aspects of polyphenolic agents in cancer therapy. They regulate specific key processes involved in cancer progression and modulate the expression of oncogenic proteins, like p27, p21, and p53, which may lead to apoptosis, cell cycle arrest, inhibition of cell proliferation, and, consequently, cancer suppression. Thus, one of the mechanisms underlying the anti-cancer activity of phenolics involves the regulation of tumor suppressor genes. Among them, the BRCA genes, with the two forms (BRCA-1 and BRCA-2), play a pivotal role in cancer protection and prevention. BRCA germline mutations are associated with an increased risk of developing several types of cancers, including ovarian, breast, and prostate cancers. BRCA genes also play a key role in the sensitivity and response of cancer cells to specific pharmacological treatments. As the importance of BRCA-1 and BRCA-2 in reducing cancer invasiveness, repairing DNA damages, oncosoppression, and cell cycle checkpoint, their regulation by natural molecules has been examined.

scholarly journals The Mechanism of Melatonin and Its Receptor MT2 Involved in the Development of Bovine Granulosa Cells

2018 ◽  
Vol 19 (7) ◽  
pp. 2028 ◽  
Author(s):  
Shujuan Wang ◽  
Wenju Liu ◽  
Xunsheng Pang ◽  
Sifa Dai ◽  
Guodong Liu
Keyword(s):  
Granulosa Cells ◽  
Regulatory Mechanism ◽  
Steroid Hormone ◽  
Inhibin B ◽  
Critical Approach ◽  
Hormone Synthesis ◽  
Ovarian Granulosa Cells ◽  
Genes Expression ◽  
Significant Difference

Ovarian granulosa cells (GCs) are a critical approach to investigate the mechanism of gene regulation during folliculogenesis. The objective of this study was to investigate the role of MT2 in bovine GCs, and assess whether MT2 silencing affected GCs response to melatonin. We found that MT2 silencing significantly decreased the secretion of progesterone and estradiol, and increased the concentration of inhibin B and activin B. To further reveal the regulatory mechanism of MT2 silencing on steroids synthesis, it was found that the expression of CYP19A1 and CYP11A1 enzymes (steroid hormone synthesis) were down-regulated, while genes related to hormonal synthesis (StAR, RUNX2, INHA and INHBB) were up-regulated without affecting the expression of INHBA, suggesting that MT2 silencing may regulate hormone abundance. Furthermore, MT2 silencing significantly increased the expression of TGFBR3 and BMP6, and decreased the expression of LHR and DNMT1A without significant difference in the expression of FSHR and EGFR. In addition, MT2 silencing didn’t affect the effect of melatonin on increasing the expression of DNMT1A, EGFR, INHBA and LHR, and progesterone level, or decreasing INHA, TGFBR3 and StAR expression, and production of inhibin B. Moreover, MT2 silencing could disrupt the role of melatonin in decreasing the FSHR, INHBB and BMP6 expression, and activin B secretion. In conclusion, these results reveal that melatonin and MT2 are essential regulator of bovine GCs function by modulating reproduction-related genes expression, hormones secretion and other regulators of folliculogenesis.

scholarly journals MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human cov434 cells by targeting FGD4

2020 ◽  
Author(s):  
Ji Lin ◽  
Huijuan Huang ◽  
Liheng Lin ◽  
Weiwei Li ◽  
Jianfen Huang
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Follicular Development ◽  
Inhibitory Effect ◽  
Luciferase Reporter ◽  
Cycle Arrest ◽  
Proliferation And Apoptosis ◽  
Regulation Of Proliferation ◽  
Healthy Control

Abstract Background: MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells. Results: Downregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway. Conclusions: In conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.

scholarly journals Silencing circ_0058063 enhances proliferation and inhibits apoptosis in PCOS ovarian granulosa cells

2021 ◽  
Author(s):  
Chengcai Wen ◽  
Li Zhang
Keyword(s):  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Endocrine Disease ◽  
Ovarian Granulosa Cells ◽  
Gene And Protein Expression ◽  
Proliferation And Apoptosis ◽  
Pcos Group ◽  
Reproductive Aged Women ◽  
Western Blotting Assay

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive-aged women. This study was designed to explore the role of circ_0058063 in PCOS.Methods We recruited nine PCOS patients and nine no-PCOS patients. The concentrations of follicle stimulating hormone (FSH), testosterone (T), luteinizing hormone (LH), progesterone (P4) and estradiol (E2) were measured by radioimmunoassay. The level of aromatase was detected using an ELISA kit. The proliferation and apoptosis of ovarian granulosa cells were assessed using CCK-8 assay and flow cytometry, respectively. Gene and protein expression were evaluated through RT-qPCR and Western blotting assay.Results The circ_0058063 level in ovarian granulosa cells and follicular fluid is significantly higher in the PCOS group than the no-PCOS group. Besides, silencing circ_0058063 increases the levels of Aromatase mRNA, P4 and E2 in PCOS ovarian granulosa cells. Additionally, silencing circ_0058063 can promote the proliferation of ovarian granulosa cells in patients with PCOS. Furthermore, silencing circ_0058063 can suppress apoptosis of PCOS ovarian granulosa cells.Conclusions Silencing circ_0058063 enhances proliferation and inhibits apoptosis in PCOS ovarian granulosa cells. Such findings may offer vital insights into a therapeutic target for PCOS.

Roles of vitamin D and its receptor in the proliferation and apoptosis of luteinised granulosa cells in the goat

2020 ◽  
Vol 32 (3) ◽  
pp. 335 ◽  
Author(s):  
Xiaolei Yao ◽  
Zhibo Wang ◽  
M. A. El-Samahy ◽  
Caifang Ren ◽  
Zifei Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Vitamin D ◽  
Granulosa Cells ◽  
Expression Patterns ◽  
Follicular Development ◽  
Proliferation Rate ◽  
Control Group ◽  
Dependent Manner ◽  
Proliferation And Apoptosis ◽  
Dose Dependent

The objective of this study was to investigate the dose-dependent effect of 1α,25-(OH)2VD3 (Vit D3) on invitro proliferation of goat luteinised granulosa cells (LGCs) and to determine the underlying mechanisms of its action by overexpressing and silencing vitamin D receptor (VDR) in LGCs. Results showed that VDR was prominently localised in GCs and theca cells (TCs) and its expression increased with follicle diameter, but was lower in atretic follicles than in healthy follicles. The proliferation rate of LGCs was significantly higher in the Vit D3-treated groups than in the control group, with the highest proliferation rate observed in the 10nM group; this was accompanied by changes in the expression of cell cycle-related genes. These data indicate that Vit D3 affects LGC proliferation in a dose-dependent manner. Contrary to the VDR knockdown effects, its overexpression upregulated and downregulated cell cycle- and apoptosis-related genes respectively; moreover, supplementation with 10nM of Vit D3 significantly enhanced these effects. These results suggest that changes in VDR expression patterns in LGCs may be associated with follicular development by regulation of cell proliferation and apoptosis. These findings will enhance the understanding of the roles of Vit D3 and VDR in goat ovarian follicular development.

scholarly journals MAPK, AKT/FoxO3a and mTOR pathways are involved in cadmium regulating the cell cycle, proliferation and apoptosis of chicken follicular granulosa cells

2021 ◽  
Vol 214 ◽  
pp. 112091
Author(s):  
Mingkun Zhu ◽  
Sasa Miao ◽  
Wenting Zhou ◽  
Shaaban Saad Elnesr ◽  
Xinyang Dong ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Granulosa Cells ◽  
Proliferation And Apoptosis

scholarly journals Kaempferol and Its Glycoside Derivatives as Modulators of Etoposide Activity in HL-60 Cells

2021 ◽  
Author(s):  
Magdalena Kluska ◽  
Michał Juszczak ◽  
Jerzy Żuchowski ◽  
Anna Stochmal ◽  
Katarzyna Woźniak
Keyword(s):  
Cell Cycle ◽  
Free Radicals ◽  
Lens Culinaris ◽  
Cell Cycle Progression ◽  
Opposite Effect ◽  
Cycle Progression ◽  
Aerial Parts ◽  
Proliferation And Apoptosis ◽  
Antitumor Properties ◽  
The Impact

Abstract Kaempferol is a polyphenol found in a variety of plants. Kaempferol has antitumor properties by affecting proliferation and apoptosis of cancer cells. We investigated whether kaempferol and its glycoside derivatives: kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D -glucuropyranoside (P2), kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P5) and kaempferol 3-O-[(6-O-E-feruloyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P7) isolated from aerial parts of Lens culinaris Medik. affect the antitumor activity of etoposide in HL-60 cells. We analyzed the effect of kaempferol and its derivatives on cytotoxicity, DNA damage, apoptosis, cell cycle progression and free radicals induced by etoposide. We also studied the impact of kaempferol and its derivatives on the expression of HO-1 and Nrf-2 genes in HL-60 cells. We demonstrated that kaempferol increases the sensitivity of HL-60 cells to etoposide but does not affect apoptosis induced by this drug. Kaempferol also reduces the level of free radicals generated by etoposide. Unlike kaempferol, some of its derivatives reduce the apoptosis of HL-60 cells (P2 and P7) and increase the level of free radicals (P2 and P5) induced by etoposide. Our results indicate that kaempferol derivatives may have an opposite effect on the action of etoposide in HL-60 cells compared to kaempferol.

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