Activation of Adenosine Monophosphate-Activated Protein Kinase Is an Additional Mechanism That Participates in Mediating Inhibitory Actions of Prostaglandin F2Alpha in Mature, but Not Developing, Bovine Corpora Lutea1

Bowdridge, Elizabeth C.; Goravanahally, Madhusudan P.; Inskeep, E. K.; Flores, Jorge A.

doi:10.1095/biolreprod.115.129411

Cited by 16 publications

(16 citation statements)

References 25 publications

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“…Taken together, these findings suggest that a Ca 2+ /CaMKKβ-AMPK-IRS1/PI3K/AKT signalling system mediates the amelioration of IR induced by exogenous NaHS, at least in our cell model. As reported previously, CaMKKβ and AMPK participate in signal transduction associated with the mature bovine corpus luteum 45 , in the generation of androgen-related prostate cancer and in the migration and invasion of prostate cancer 46 . In addition, the CaMKKβ-AMPK pathway also plays a role in the signalling network that regulates adipocyte development 47 .…”

Section: Discussionsupporting

confidence: 55%

Hydrogen Sulphide Treatment Increases Insulin Sensitivity and Improves Oxidant Metabolism through the CaMKKbeta-AMPK Pathway in PA-Induced IR C2C12 Cells

Chen

Zhao

Lan

et al. 2017

Sci Rep

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Studies have reported attenuation of insulin resistance (IR) by improving phosphorylation of the insulin signalling pathway. However, the upstream molecular signalling pathway is still elusive. In this study, Western blot was used to evaluate the phosphorylation level of the insulin signalling pathway and the AMPK pathway. 2-NBDG was used to evaluate glucose uptake. Ca2+ imaging was used to assess change of intracellular Ca2+ concentration. We found that NaHS enhanced the intracellular Ca2+ concentration and glucose uptake and activated the insulin signalling cascade in a palmitic acid (PA)-induced IR model in C2C12 cells. Furthermore, activation of the IRS1/PI3K/AKT pathway and glucose uptake were decreased when AMPK or CaMKKβ was inhibited. Our study also showed that the mitochondrial electron transport chain, ATP production, and intramitochondrial cAMP declined in the IR model but that this effect was reversed by NaHS, an effect that may be mediated by the Ca2+/CaMKK2/AMPK and PI3K/AKT pathways. Our data indicate that H2S improves activation of the insulin signalling cascade and glucose uptake via activation of the Ca2+/CaMKK2/AMPK pathway and mitochondrial metabolism in C2C12 cells. Furthermore, NaHS protects mitochondrial function and maintains normal ATP production by activating the cAMP system and the Ca2+/CaMKK2/AMPK and PI3K/ATK pathways.

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Section: Discussionsupporting

confidence: 55%

Hydrogen Sulphide Treatment Increases Insulin Sensitivity and Improves Oxidant Metabolism through the CaMKKbeta-AMPK Pathway in PA-Induced IR C2C12 Cells

Chen

Zhao

Lan

et al. 2017

Sci Rep

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“…51 Treatment of large luteal cells with either PGF2α or PMA leads to activation of ERK signaling via PKC, 52 and ultimately apoptosis. [72][73][74] Furthermore, PGF2α actives AMPK in bovine large luteal cells, 75 which could recruit DRP1 to mitochondria. Caution is needed with this speculation because studies have demonstrated opposing effects of AMPK on DRP1, both inhibiting [76][77][78][79][80] and promoting DRP1-mediated mitochondrial fission.…”

Section: Discussionmentioning

confidence: 99%

Luteinizing hormone regulates the phosphorylation and localization of the mitochondrial effector dynamin‐related protein‐1 (DRP1) and steroidogenesis in the bovine corpus luteum

et al. 2020

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The corpus luteum is an endocrine gland that synthesizes and secretes progesterone. Luteinizing hormone (LH) activates protein kinase A (PKA) signaling in luteal cells, increasing delivery of substrate to mitochondria for progesterone production. Mitochondria maintain a highly regulated equilibrium between fusion and fission in order to sustain biological function. Dynamin‐related protein 1 (DRP1), is a key mediator of mitochondrial fission. The mechanism by which DRP1 is regulated in the ovary is largely unknown. We hypothesize that LH via PKA differentially regulates the phosphorylation of DRP1 on Ser616 and Ser637 in bovine luteal cells. In primary cultures of steroidogenic small luteal cells (SLCs), LH, and forskolin stimulated phosphorylation of DRP1 (Ser 637), and inhibited phosphorylation of DRP1 (Ser 616). Overexpression of a PKA inhibitor blocked the effects of LH and forskolin on DRP1 phosphorylation. In addition, LH decreased the association of DRP1 with the mitochondria. Genetic knockdown of the DRP1 mitochondria receptor, and a small molecule inhibitor of DRP1 increased basal and LH‐induced progesterone production. Studies with a general Dynamin inhibitor and siRNA knockdown of DRP1 showed that DRP1 is required for optimal LH‐induced progesterone biosynthesis. Taken together, the findings place DRP1 as an important target downstream of PKA in steroidogenic luteal cells.

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“…In agreement with the findings in cattle and rats, treatment with AICAR resulted in a significant decrease in basal P4 at all concentrations tested in experiment 1. Similarly, AICAR treatment resulted in a decrease in P4 production in the mature bovine CL [ 4 ]. This decrease in P4 could be explained, at least in part, by a decrease in key enzymes such as 3βHSD, P450scc, or StAR, all of which have been shown to be decreased after treatment with AICAR in rat granulosa cells [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranoside [AICAR] is a well-established, cell-permeable agent, which both directly activates AMPK alloterically and promotes phosphorylation of AMPK [ 7 ]. Treatment with AICAR (7.5 mM) significantly decreased basal P4 production in bovine CL in vitro [ 4 ]. In contrast, dorsomorphin dihydrochloride (DM) is a potent, selective, cell-permeable and reversible AMPK inhibitor [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

In vitro progesterone production by luteinized human mural granulosa cells is modulated by activation of AMPK and cause of infertility

Bowdridge

Vernon

Flores

et al. 2017

Reprod Biol Endocrinol

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BackgroundMural granulosa cells from IVF patients were provided by the West Virginia University Center for Reproductive Medicine in Morgantown, WV. The effect of adenosine monophosphate activated protein kinase (AMPK) activation, primary cause of infertility, age, BMI, and pregnancy outcome on production of progesterone were examined separately.MethodsIsolated mural sheets from IVF patients (n = 26) were centrifuged, supernatant discarded, and the pellet re-suspended in 500 μl of DMEM/F12. Mural granulosa cells were plated at 10,000 cells/well in triplicate per treatment group with 300 μl DMEM/F12 media at 37 °C and 5% CO2 in a humidified incubator to permit luteinization. Four days after initial plating, cells were treated with either an AMPK inhibitor, DM; an AMPK activator, AICAR; or hCG. Cells were cultured for 24 h after treatment when medium was collected and frozen at −20 °C until assayed for P4 by radioimmunoassay.ResultsThe AMPK activator, AICAR, inhibited P4 production (P < 0.001), whereas the AMPK inhibitor, DM, did not affect basal P4 (P < 0.05). Progesterone production increased when cells from patients whose primary cause of infertility was a partner having male infertility were treated with hCG compared to control (P = 0.0045), but not in patients with other primary infertility factors (P > 0.05). Additionally, hCG increased P4 production in patients between the ages 30–35 (P = 0.008) and 36–39 (P = 0.04), but not in patients ages 25–29 (P = 0.73). Patients with normal BMI had increased P4 production when treated with hCG (P < 0.0001), however there was no change in P4 production from cells of patients who were overweight or obese (P > 0.05). Cells from patients who became pregnant to IVF had greater P4 production when stimulated with hCG than those who did not become pregnant when compared to controls (P > 0.05).ConclusionsUnderstanding how AMPK activation is regulated in ovarian cells could lead to alternative or novel infertility treatments. Human mural granulosa cells can serve as a valuable model for understanding how AMPK affects P4 production in steroidogenic cells. Additionally, when stimulated with hCG, P4 production by mural granulosa cells differed among infertility type, age, BMI, and pregnancy outcome.Electronic supplementary materialThe online version of this article (10.1186/s12958-017-0295-9) contains supplementary material, which is available to authorized users.

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Activation of Adenosine Monophosphate-Activated Protein Kinase Is an Additional Mechanism That Participates in Mediating Inhibitory Actions of Prostaglandin F2Alpha in Mature, but Not Developing, Bovine Corpora Lutea1

Cited by 16 publications

References 25 publications

Hydrogen Sulphide Treatment Increases Insulin Sensitivity and Improves Oxidant Metabolism through the CaMKKbeta-AMPK Pathway in PA-Induced IR C2C12 Cells

Hydrogen Sulphide Treatment Increases Insulin Sensitivity and Improves Oxidant Metabolism through the CaMKKbeta-AMPK Pathway in PA-Induced IR C2C12 Cells

Luteinizing hormone regulates the phosphorylation and localization of the mitochondrial effector dynamin‐related protein‐1 (DRP1) and steroidogenesis in the bovine corpus luteum

In vitro progesterone production by luteinized human mural granulosa cells is modulated by activation of AMPK and cause of infertility

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