Effects of Circadian Rhythm Hormones Melatonin and 5-Methoxytryptophol on COXs, Raf-1 and STAT3

Savtekin, Gokce; Serakıncı, Nedime; Erzik, Can; Çetınel, Şule; Şehirli, Ahmet Özer

doi:10.3923/ijp.2018.787.795

Cited by 7 publications

(12 citation statements)

References 32 publications

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“…The present study shows that the RAF1 stimulates E 2 synthesis and secretion via FSH signaling pathway in mouse GCs. Previous reports have shown that RAF involved in the regulation of steroid hormone synthesis via ERK1/2 [23] or affected the functions of steroid hormones and their receptors [25], and its interacted with microRNA [24]. The present study demonstrated RAF1 acted as a molecule of FSH pathway to trigger the ERK phosphorylation and stimulate GCs estradiol synthesis and secretion events.…”

Section: Discussionsupporting

confidence: 59%

RAF1 as Downstream Molecule Mediates the FSH Signaling Pathway to Stimulate E2 Synthesis and Secretion in Mouse Ovarian Granulosa Cells

Luo

Liu

Guo

et al. 2020

Preprint

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Background: V-raf-leukemia viral oncogene 1 (RAF1) kinase is the key factor in extracellular signal regulated pathway, which transmits signals to the downstream extracellular regulated protein kinases (ERK). Regulatory function of RAF1 has been proved to mediate steroid hormone synthesis, which played an essential physiological function in reproduction and development. Whether RAF1 takes part in the signaling events of gonadotropic hormones follicle-stimulating hormone (FSH) in ovarian is unknown.Results: We found that RAF1 as downstream molecule mediates the FSH signaling pathway to stimulate estradiol (E2) synthesis and secretion in mouse ovarian granulosa cells (GCs). The expression of RAF1 is induced by FSH and the production of E2 is increased in the serum and primary ovarian GCs supernatant, the process of which is blocked by treating with RAF1 inhibitor (N-(2-Methyl-5'-morpholino-6'-((tetrahydro-2H-pyran-4-yl)oxy)-[3,3'-bipyridin]-5-yl)-3(trifluoromethyl) benzamide, RAF709). Inhibition of RAF1 activity by RAF709 decreased ERK phosphorylation, and suppressed the expression of cytochrome P450 family 19 subfamily a member 1 (CYP19A1) which is a major rate-limiting enzyme to participate in the last step of E2 biosynthesis. Conclusion: Our results suggest that RAF1 play a pivotal mediating roles toward E2 production in FSH signaling pathway by inducing the phosphorylation of ERK and promoting the process of estradiol synthesis. RAF1 may be a potential and effective factor to regulate the function of the female mouse reproductive system.

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Section: Discussionsupporting

confidence: 59%

RAF1 as Downstream Molecule Mediates the FSH Signaling Pathway to Stimulate E2 Synthesis and Secretion in Mouse Ovarian Granulosa Cells

Luo

Liu

Guo

et al. 2020

Preprint

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“…Despite the absence of studies investigating melatonin use in COVID-19 patients, melatonin administration has yielded promising outcomes through suppressing the circulating cytokine levels in other diseases and in cases with elevated inflammation levels [ 51 , 56 , 57 ]. Melatonin was shown to stimulate a significant decline in serum MMP, TNF-α, IFN-γ, IL-6, MCP-1 and C-reactive protein (CRP) levels in experimental and clinical studies [ 58 , 59 ]. These mediators are known to have a critical role in CD147-mediated inflammation pathway.…”

Section: The Antiviral Effect Of Melatonin Through Cd147mentioning

confidence: 99%

Role of melatonin in the treatment of COVID-19; as an adjuvant through cluster differentiation 147 (CD147)

2020

Self Cite

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COVID-19 caused by the SARS-CoV-2 outbreak quickly has turned into a pandemic. However, no specific antiviral agent is yet available. In this communication, we aimed to evaluate the significance of CD147 protein and the potential protective effect of melatonin that is mediated by this protein in COVID-19. CD147 is a glycoprotein that is responsible for the cytokine storm in the lungs through the mediation of viral invasion. Melatonin use previously was shown to reduce cardiac damage by blocking the CD147 activity. Hence, melatonin, a safe drug, may prevent severe symptoms, reduce symptom severity and the adverse effects of the other antiviral drugs in COVID-19 patients. In conclusion, the use of melatonin, which is reduced in the elderly and immune-compromised patients, should be considered as an adjuvant through its CD147 suppressor and immunomodulatory effect.

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“…Besides, the production of 5-MTX in summer is higher at night than in winter due to the photoperiod in summer [3] . Considering the physiological effects of 5-MTX, we hypothesied that the 5-MTX could be a possible treatment agent against COVID-19 through its antioxidant and immunomodulatory mechanisms [4] , [5] .…”

Section: Hyptohesismentioning

confidence: 99%

“…In the study conducted by Savtekin et al, It was revealed that 5-MTX both prevented synovial inflammation and suppressed the development of temporomandibular arthritis, similar to melatonin. In these studies, it has been shown that 5-MTX inhibits the activation of matrix metalloproteinases 2 and 8, TNF-α and IL-1β and Rapidly Accelerated Fibrosarcoma 1 (RAF-1), Signal Transducer and Activator of Transcription 3 (STAT-3) and Cyclooxygenase-2 (COX-2) [4] , [5] . Lissoni et al [7] suggests that 5-MTX and melatonin should be used together to be protected for 24 h since the secretion of 5-MTX in the daytime and the secretion of melatonin at night increase.…”

Section: -Methoxytryptophol (5-mtx)mentioning

confidence: 99%

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Daylight is critical to preserve 5-methoxytryptophol levels in suspected and confirmed COVID-19 patients

Şehirli

Sayıner

2021

Medical Hypotheses

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Effects of Circadian Rhythm Hormones Melatonin and 5-Methoxytryptophol on COXs, Raf-1 and STAT3

Cited by 7 publications

References 32 publications

RAF1 as Downstream Molecule Mediates the FSH Signaling Pathway to Stimulate E2 Synthesis and Secretion in Mouse Ovarian Granulosa Cells

RAF1 as Downstream Molecule Mediates the FSH Signaling Pathway to Stimulate E2 Synthesis and Secretion in Mouse Ovarian Granulosa Cells

Role of melatonin in the treatment of COVID-19; as an adjuvant through cluster differentiation 147 (CD147)

Daylight is critical to preserve 5-methoxytryptophol levels in suspected and confirmed COVID-19 patients

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