Journal: Journal of pineal research

Article Title: Biological effects of melatonin on osteoblast/osteoclast cocultures, bone, and quality of life: Implications of a role for MT2 melatonin receptors, MEK1/2, and MEK5 in melatonin-mediated osteoblastogenesis.

doi: 10.1111/jpi.12465

Figure Lengend Snippet: FIGURE 11 Proposed mechanisms underlying melatonin’s actions on osteoblastogenesis and osteoclastogenesis. As shown, melatonin, via MT2 melatonin receptors, modulates osteoblastogenesis by coupling to both MEK1/2 and MEK5. Stimulation of MT2 melatonin receptors by melatonin in osteoblasts leads to activation of MEK5 resulting in increases in pERK5, RUNX2, NFκB, and GLUT4. MT2 melatonin receptor-mediated activation of MEK1/2 leads to increases in pERK1/2 and decreases in PPARγ, GLUT4, and IRβ. It is proposed that cross talk between MEK1/2 and MEK5 may occur where MEK5 negative regulates MEK1/2 only when both kinases are inhibited simultaneously. In MSCs, melatonin/MT2R-mediated decreases in PPARγ levels shift MSCs away from adipogenesis and toward osteogenesis. Following MSC differentiation into osteoblasts by melatonin, the mature osteoblasts begin secreting OPG to inhibit osteoclastogenesis from PBMCs

Article Snippet: For the inhibitor studies, cells were treated with 1 μmol/L of the MT2 melatonin receptor antagonist, 4P- PDOT (Tocris), 3 μmol/L of the MEK1/2 inhibitor, PD898059 (SantaCruz Biotechnology, USA), 10 μmol/L of the MEK5 inhibitor, BIX02189 (SantaCruz Biotechnology, Dallas, TX, USA), or 10 μmol/L of SC- 1- 151, a MEK1/2 and MEK5 inhibitor (generous gift from Dr. Patrick Flaherty; https://www.google.com/patents/ WO2015038743A1?cl=en) either alone or in combination with melatonin.

Techniques: Activation Assay

Journal: International journal of molecular sciences

Article Title: Melatonin Receptor Expression in Primary Uveal Melanoma.

doi: 10.3390/ijms25168711

Figure Lengend Snippet: Figure 2. MTNR1A and MTNR1B receptors in the nucleus vs. cytoplasm. (A) The mean optical density (OD) for MTNR1A was significantly higher in the cytoplasm compared to the nucleus (p < 0.0001, n = 46); (B) The mean optical density (OD) for MTNR1B was significantly higher in the cytoplasm compared to the nucleus (p < 0.0001, n = 45).

Article Snippet: Formalin-fixed paraffin-embedded tissue from the enucleated eyes were sectioned and stained on a BOND III IHC stainer by biomedical analysts using mouse monoclonal antibodies to detect melatonin receptor 1A (NBP3-03633, Novus Biologicals, Centennial, CO, USA) and melatonin receptor 1B (NLS932, Novus Biologicals, Centennial, CO, USA).

Techniques:

Journal: International journal of molecular sciences

Article Title: Melatonin Receptor Expression in Primary Uveal Melanoma.

doi: 10.3390/ijms25168711

Figure Lengend Snippet: Figure 3. Kaplan–Meier survival curves and scatter plots for MTNR1B expression. (A) Survival curve comparing the incidence of UM-related death in those with MTNR1B OD levels in the nucleus below or equal to and above the median value (p = 0.98), n = 45. (B) Survival curve comparing incidence of UM-related death in those with MTNR1B OD levels in the cytoplasm below or equal to and above the median value (p = 0.34), n = 45. (C) Scatter plot comparing MTNR1B RNA expression in patient tumors with disomy 3 or monosomy 3. (D) Scatter plot comparing MTNR1B RNA expression in patients with tumors of an epithelioid cell type compared to other cell types (spindle or mixed). (E) Scatter plot comparing MTNR1B RNA expression in patients with the BAP1 wild type or BAP1 mutation. (F) Scatter plot comparing MTNR1B OD levels in the nucleus of tumor cells for patients who did or did not die due to uveal melanoma. (G) Scatter plot comparing MTNR1B OD levels in the cytoplasm of tumor cells for patients who did or did not die due to uveal melanoma. Colored fields on the Kaplan–Meier curves indicate 95% confidence intervals. ns = not significant. TCGA cohort, St Erik cohort.

Article Snippet: Formalin-fixed paraffin-embedded tissue from the enucleated eyes were sectioned and stained on a BOND III IHC stainer by biomedical analysts using mouse monoclonal antibodies to detect melatonin receptor 1A (NBP3-03633, Novus Biologicals, Centennial, CO, USA) and melatonin receptor 1B (NLS932, Novus Biologicals, Centennial, CO, USA).

Techniques: Expressing, RNA Expression, Mutagenesis