The cAMP Analogue, dbcAMP, Affects Rabbit Ovarian Cell Proliferation, Apoptosis, Release of Steroids and Response to Hormones

Sirotkin, Alexander V.; Baláži, Andrej; Chrenek, Peter

doi:10.3409/fb62_3.211

Cited by 9 publications

(5 citation statements)

References 28 publications

(73 reference statements)

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“…These increases in cell proliferation and death suggest that bee pollen can promote ovarian cell turnover. Similar stimulatory actions on cultured ovarian cell turnover has been previously reported: promotion of both proliferation and apoptosis was observed in known regulators of ovarian functions such as follicle stimulating hormone (Sirotkin et al 2014(Sirotkin et al , 2017, leptin (Sirotkin et al 2012), IGF-I and ghrelin (Sirotkin et al 2014), some siRNAs controlling ovarian cell protein kinases (Sirotkin et al 2010), iron (Kolesarova et al 2011b), and the plant isoflavone daidzein (Sirotkin et al 2017) which is present in bee pollen (Denisow and Denisow-Pietrzyk 2016;Cornara et al 2017;Kieliszek et al 2018). Therefore, daidzein is one component that could be responsible for the effects of bee pollen on the ovary.…”

Section: Does Bee Pollen Directly Affect Ovarian Cell Viability?supporting

confidence: 83%

Bee pollens originating from different species have unique effects on ovarian cell functions

Sirotkin

Tarko

Alexa

et al. 2020

Pharmaceutical Biology

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Context: The species-specific differences and mechanisms of action of bee pollen on reproduction have not been well studied. Objective: We compared the effects of bee pollen extracts from different plants on ovarian cell functions. Materials and methods: We compared the effects of pollens from black alder, dandelion, maize, rapeseed, and willow at 0, 0.01, 0.1, 1, 10, or 100 mg/mL on cultured porcine ovarian granulosa cells. Cell viability was assessed with a Trypan blue test, the cell proliferation marker (PCNA), and an apoptosis marker (BAX) were assessed by immunocytochemistry. Insulin-like growth factor (IGF-I) release was measured by an enzyme-linked immunosorbent assay. Results: Addition of any bee pollen reduced cell viability, promoted accumulation of both proliferation and apoptosis markers, and promoted IGF-I release. The ability of various pollens to suppress cell viability ranked as follows: rapeseed > dandelion > alder > maize > willow. The biological activity of bee pollens regarding their stimulatory action on ovarian cell proliferation ranked as follows: dandelion > willow > maize > alder > rapeseed. Cell apoptosis was promoted by pollens as follows: range > dandelion > alder > rapeseed > willow > maize. The ability of the pollens to stimulate IGF-I output are as follows: willow > dandelion > rapeseed > maize > alder. Discussion: Bee pollen can promote ovarian cell proliferation by promoting IGF-I release, but it induces the dominance of apoptosis over proliferation and the reduction in ovarian cell viability in a species-specific manner. Conclusions: This is the first demonstration of adverse effects of bee pollen on ovarian cell viability and of its direct stimulatory influence on proliferation, apoptosis, and IGF-I release. The biological potency of bee pollen is dependent on the plant species.

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Section: Does Bee Pollen Directly Affect Ovarian Cell Viability?supporting

confidence: 83%

Bee pollens originating from different species have unique effects on ovarian cell functions

Sirotkin

Tarko

Alexa

et al. 2020

Pharmaceutical Biology

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“…As discussed earlier we and others have demonstrated that SIRT1 activation enhances cAMP levels [12,56,57]. Perhaps surprisingly, quite a few studies had linked elevated intracellular levels of cAMP to apoptosis in various cell types [77][78][79] including ovarian follicular cells and GCs [80][81][82][83]. For instance, it was shown that treatment of GCs with forskolin, or 8-bromo-cAMP induced apoptosis as evidenced by DNA fragmentation and chromatin condensation.…”

Section: Discussionmentioning

confidence: 88%

Diverse actions of sirtuin-1 on ovulatory genes and cell death pathways in human granulosa cells

Sapuleni

Szymańska

Meidan

2022

Reprod Biol Endocrinol

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Background Human granulosa-lutein cells (hGLCs) amply express sirtuin-1 (SIRT1), a NAD + -dependent deacetylase that is associated with various cellular functions. SIRT1 was shown to elevate cAMP on its own and additively with human chorionic gonadotropin (hCG), it is therefore interesting to examine if SIRT1 affects other essential hGLC functions. Methods Primary hGLCs, obtained from the follicular aspirates of women undergoing IVF and SV40-transfected, immortalized hGLCs (SVOG cells), were used. Primary cells were treated with SIRT1 specific activator SRT2104, as well as hCG or their combination. Additionally, siRNA-targeting SIRT1 construct was used to silence endogenous SIRT1 in SVOG cells. PTGS2, EREG, VEGFA and FGF2 expression was determined using quantitative polymerase chain reaction (qPCR). Apoptotic and necroptotic proteins were determined by specific antibodies in western blotting. Cell viability/apoptosis was determined by the XTT and flow cytometry analyses. Data were analyzed using student t-test or Mann–Whitney U test or one-way ANOVA followed by Tukey HSD post hoc test. Results In primary and immortalized hGLCs, SRT2104 significantly upregulated key ovulatory and angiogenic genes: PTGS2, EREG, FGF2 and VEGFA, these effects tended to be further augmented in the presence of hCG. Additionally, SRT2104 dose and time-dependently decreased viable cell numbers. Flow cytometry of Annexin V stained cells confirmed that SIRT1 reduced live cell numbers and increased late apoptotic and necrotic cells. Moreover, we found that SIRT1 markedly reduced anti-apoptotic BCL-XL and MCL1 protein levels and increased cleaved forms of pro-apoptotic proteins caspase-3 and PARP. SIRT1 also significantly induced necroptotic proteins RIPK1 and MLKL. RIPK1 inhibitor, necrostatin-1 mitigated SIRT1 actions on RIPK1 and MLKL but also on cleaved caspase-3 and PARP and in accordance on live and apoptotic cells, implying a role for RIPK1 in SIRT1-induced cell death. SIRT1 silencing produced inverse effects on sorted cell populations, anti-apoptotic, pro-apoptotic and necroptotic proteins, corroborating SIRT1 activation. Conclusions These findings reveal that in hGLCs, SIRT1 enhances the expression of ovulatory and angiogenic genes while eventually advancing cell death pathways. Interestingly, these seemingly contradictory events may have occurred in a cAMP-dependent manner.

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“…In the ovaries, cAMP is of utmost importance as a second messenger for growth and development of follicles in all stages [30][31][32]. Studies revealed that cAMP response element-binding protein 1 (creb1) and the cAMP analogue, dbcAMP were involved in the down-regulation of porcine and rabbit ovarian cell proliferation, respectively [33,34]. In addition, cAMP inhibited rat hepatocellular carcinoma cell proliferation and enhanced cell differentiation [35].…”

Section: Discussionmentioning

confidence: 99%

Regulation of Female Folliculogenesis by Tsp1a in Nile Tilapia (Oreochromis niloticus)

Jie

Zhou

et al. 2020

IJMS

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TSP1 was reported to be involved in multiple biological processes including the activation of TGF-β signaling pathways and the regulation of angiogenesis during wound repair and tumor growth, while its role in ovarian folliculogenesis remains to be elucidated. In the present study, Tsp1a was found to be expressed in the oogonia and granulosa cells of phase I to phase IV follicles in the ovaries of Nile tilapia by immunofluorescence. tsp1a homozygous mutants were generated by CRISPR/Cas9. Mutation of tsp1a resulted in increased oogonia, reduced secondary growth follicles and delayed ovary development. Expression of the cell proliferation marker PCNA was significantly up-regulated in the oogonia of the mutant ovaries. Furthermore, transcriptomic analysis revealed that expressions of DNA replication related genes were significantly up-regulated, while cAMP and MAPK signaling pathway genes which inhibit cell proliferation and promote cell differentiation were significantly down-regulated. In addition, aromatase (Cyp19a1a) expression and serum 17β-estradiol (E2) concentration were significantly decreased in the mutants. These results indicated that lacking tsp1a resulted in increased proliferation and inhibited differentiation of oogonia, which in turn, resulted in increased oogonia, reduced secondary growth follicles and decreased E2. Taken together, our results indicated that tsp1a was essential for ovarian folliculogenesis in Nile tilapia.

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The cAMP Analogue, dbcAMP, Affects Rabbit Ovarian Cell Proliferation, Apoptosis, Release of Steroids and Response to Hormones

Cited by 9 publications

References 28 publications

Bee pollens originating from different species have unique effects on ovarian cell functions

Bee pollens originating from different species have unique effects on ovarian cell functions

Diverse actions of sirtuin-1 on ovulatory genes and cell death pathways in human granulosa cells

Regulation of Female Folliculogenesis by Tsp1a in Nile Tilapia (Oreochromis niloticus)

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