Isorhamnetin Promotes Estrogen Biosynthesis and Proliferation in Porcine Granulosa Cells via the PI3K/Akt Signaling Pathway

2021 ◽  
Author(s):  
Xiaoya Li ◽  
Huali Chen ◽  
Zelin Zhang ◽  
Dejun Xu ◽  
Jiaxin Duan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Porcine Granulosa Cells ◽  
Estrogen Biosynthesis

scholarly journals Isorhamnetin Protects Zearalenone-induced Damage via the PI3K/Akt Signaling Pathway in Porcine Granulosa Cells

2021 ◽  
Author(s):  
Xiaoya Li ◽  
Huali Chen ◽  
Zelin Zhang ◽  
Xiaodi Li ◽  
Jiaxin Duan ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Animal Reproduction ◽  
Bax Protein ◽  
Porcine Granulosa Cells ◽  
Cereal Grain ◽  
Induced Apoptosis ◽  
And Oxidative Stress

Abstract Background: Zearalenone (ZEA) is widely derived from moldy cereal grain, which has adverse effects on animal reproduction. In particular, pigs are more sensitive to ZEA-induced toxicity than other animals. Isorhamnetin, a flavonoid has extensive of pharmacological activities. However, little is known about the effects of isorhamnetin on reproduction. Thus, it would be interesting to clarify the effect and the underlying molecular mechanism of isorhamnetin involvement in ZEA-induced cytotoxicity in porcine granulosa cells.Results: Our findings showed that isorhamnetin suppressed ZEA-induced apoptosis by regulating Bcl-2 and Bax protein changes. Changes in intracellular Ca2+ levels and CHOP, ATF6, GRP78 indicated that isorhamnetin rescued ZEA-induced endoplasmic reticulum stress (ERS). Furthermore, isorhamnetin prevented ZEA-induced reactive oxygen species (ROS) via P38 signaling pathway. Mechanistically, isorhamnetin stimulated the expression of PCNA and CyclinD, thereby raising the ratio of S phases cells in response to ZEA-induced apoptosis via PI3K/Akt signaling pathway. Isorhamnetin also recovered ZEA-induced steroidogenesis disorder by regulating steroidogenic enzyme gene and proteins (FSH-R, CYP19A1). Conclusions: Collectively, these findings show that isorhamnetin protects granulosa cells from ZEA-induced damage via the PI3K/Akt signaling pathway, which promotes proliferation, alleviates steroidogenesis disorder, ERS and oxidative stress.

scholarly journals USP25 Regulates the Proliferation and Apoptosis of Ovarian Granulosa Cells in Polycystic Ovary Syndrome by Modulating the PI3K/AKT Pathway via Deubiquitinating PTEN

2021 ◽  
Vol 9 ◽  
Author(s):  
Yue Gao ◽  
Jiao Chen ◽  
Rui Ji ◽  
Jinli Ding ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Granular Cell ◽  
Akt Signaling ◽  
Pten Expression ◽  
Akt Signaling Pathway ◽  
Proliferation And Apoptosis ◽  
Major Factors

Background: Polycystic ovarian syndrome (PCOS) is an endocrine-related disease related to abnormal folliculogenesis and is a leading cause of infertility worldwide. Inhibition of granulosa cells (GCs) proliferation and increased GCs apoptosis have been identified as the major factors in aberrant follicle maturation.Methods: USP25 and PTEN expression in GCs from women with and without PCOS was analyzed using Western blotting. A PCOS-like mouse model was constructed using USP25 knockout and wild-type mice to explore the role of USP25 in PCOS. The human granular cell line KGN was cultured for proliferation and apoptosis assays, and the effect of USP25 on PTEN was investigated after transfection with shRNA-USP25 lentivirus.Results: USP25 expression was found to be elevated in patients and mice with PCOS. With mouse model, we observed a reduction in PCOS symptoms in mice after USP25 deletion. Increased proliferation, reduced apoptosis, activation of the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and decreased PTEN expression were found in KGN cells after USP25 knockdown. Finally, we verified that USP25 could deubiquitinate PTEN in KGN cells.Conclusions: In this study, we investigated that USP25 can regulate the PI3K/AKT signaling pathway by deubiquitinating PTEN, thus affecting the proliferation and apoptosis of GCs and contributing to the pathogenesis of PCOS.

Putative Role of the Phosphatidylinositol 3-Kinase���??Akt Signaling Pathway in the Survival of Granulosa Cells

Endocrine ◽  
2000 ◽  
Vol 12 (3) ◽  
pp. 315-321 ◽  
Author(s):  
Suzanne D. Westfall ◽  
Isabel R. Hendry ◽  
Kevin L. Obholz ◽  
Bo R. Rueda ◽  
John S. Davis
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Putative Role ◽  
Phosphatidylinositol 3

scholarly journals Acupuncture Reduces Apoptosis of Granulosa Cells in Rats with Premature Ovarian Failure Via Restoring the PI3K/Akt Signaling Pathway

2019 ◽  
Vol 20 (24) ◽  
pp. 6311 ◽  
Author(s):  
Shiqi Wang ◽  
Shujun Lin ◽  
Mingmin Zhu ◽  
Chenglu Li ◽  
Shulian Chen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Premature Ovarian Failure ◽  
Akt Signaling ◽  
Ovarian Failure ◽  
Acupuncture Group ◽  
Female Rats ◽  
Akt Signaling Pathway ◽  
Expression Levels

Acupuncture is widely recognized as an effective therapy for premature ovarian failure (POF) in clinical, but information about its potential mechanisms is rarely explored. To investigate the mechanism, fifty SD female rats were randomly divided into normal group, POF group, POF+estradiol-valerate group (abbreviated as estradiol group), and POF+acupuncture group (abbreviated as acupuncture group). The estrous cycle of the rats was tracked by vaginal smears. Their ovaries morphology was observed by hematoxylin-eosin staining. The apoptotic level of granulosa cells was detected by in situ TUNEL fluorescence staining assay. Serum follicle-stimulating hormone (FSH) and estrogen (E2) levels were measured by enzyme-linked-immunosorbent-assay (ELISA). Protein and gene expression of PI3K, Akt, bcl-2, and bax were detected by Western blotting and qPCR. In the acupuncture and estradiol groups, compared with the POF group as controls, the apoptosis number of granulosa cells was significantly decreased (p < 0.05). FSH levels were decreased, while E2 levels were increased (p > 0.05). The gene and protein expression levels of PI3K, Akt, and bcl-2 were increased, while the expression levels of bax were decreased (p < 0.05), and the protein expression level of p-Akt increased. There was no significant difference between the acupuncture group and the estradiol group (p > 0.05). Acupuncture was able to regulate hormone levels in POF rats, up-regulate PI3K/Akt signaling pathway, and reduce the apoptosis of granulosa cells. This may be one of the mechanisms of acupuncture treating premature ovarian failure.

scholarly journals Small extracellular vesicles derived from embryonic stem cells restore ovarian function of premature ovarian failure through PI3K/AKT signaling pathway

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Mengyu Liu ◽  
Yu Qiu ◽  
Zhuowei Xue ◽  
Ruoyu Wu ◽  
Jie Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Premature Ovarian Failure ◽  
Ovarian Function ◽  
Embryonic Stem ◽  
Akt Signaling ◽  
Akt Signaling Pathway

Abstract Background Premature ovarian failure (POF) has a great impact on reproductive endocrine function in females, and it is an important cause of infertility. Previous studies have demonstrated that small extracellular vesicles (sEVs) derived from stem cells play an important role in tissue regeneration. This study aimed to investigate the therapeutic effect of sEVs derived from embryonic stem cells (ESCs-sEVs) on damaged ovaries and explore the underlying molecular mechanisms. Methods Mice POF models were established by injecting mice with cyclophosphamide and busulfan. Then, ESCs-sEVs were intravenously transplanted into POF mice. The plasma of mice was harvested at 1 and 2 weeks after treatment to analyze the levels of anti-Mullerian hormone (AMH), estradiol (E2), and follicle stimulating hormone (FSH) by ELISA. The morphology of ovaries and follicles was observed by H&E staining, and apoptosis of granulosa cells was detected by TUNEL. In vitro, EdU and CCK-8 tests were used to evaluate the proliferation of cultured granulosa cells stimulated by ESCs-sEVs. Western blotting was used to determine the expression of PI3K/AKT and apoptotic-related proteins. Results After transplantation of ESCs-sEVs, the levels of serum sex hormones recovered to normal levels. In addition, the number of follicles was significantly increased, and the number of apoptotic cells was decreased. The results in vitro revealed that ESCs-sEVs could significantly improve the proliferation rate of granulosa cells and increase the expression of phosphorylated PI3K and AKT. Meanwhile, the positive effect on proliferation and the negative effect on apoptosis observed in granulosa cells were obviously decreased when the PI3K/AKT signaling pathway was inhibited. Conclusion Our findings suggested that ESCs-sEVs could improve ovarian function by regulating the PI3K/AKT signaling pathway, which could provide a promising clinical therapy for POF.

Biological role of AKT, and regulation of AKT signaling pathway by thymoquinone: perspectives in cancer therapeutics

2020 ◽  
Vol 20 ◽  
Author(s):  
Md. Junaid ◽  
Yeasmin Akter ◽  
Syeda Samira Afrose ◽  
Mousumi Tania ◽  
Md. Asaduzzaman Khan
Keyword(s):  
Clinical Trials ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Inhibitory Effect ◽  
Akt Signaling ◽  
Review Article ◽  
Therapeutic Drug ◽  
Akt Signaling Pathway ◽  
Anti Cancer

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

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