Mel1c Mediated Monochromatic Light-Stimulated IGF-I Synthesis through the Intracellular Gαq/PKC/ERK Signaling Pathway

Abstract

Previous studies have demonstrated that monochromatic light affects plasma melatonin (MEL) levels, which in turn regulates hepatic insulin-like growth factor I (IGF-I) secretion via the Mel1c receptor. However, the intracellular signaling pathway initiated by Mel1c remains unclear. In this study, newly hatched broilers, including intact, sham operation, and pinealectomy groups, were exposed to either white (WL), red (RL), green (GL), or blue (BL) light for 14 days. Experiments in vivo showed that GL significantly promoted plasma MEL formation, which was accompanied by an increase in the MEL receptor, Mel1c, as well as phosphorylated extracellular regulated protein kinases (p-ERK1/2), and IGF-I expression in the liver, compared to the other light-treated groups. In contrast, this GL stimulation was attenuated by pinealectomy. Exogenous MEL elevated the hepatocellular IGF-I level, which is consistent with increases in cyclic adenosine monophosphate (cAMP), Gαq, phosphorylated protein kinase C (p-PKC), and p-ERK1/2 expression. However, the Mel1c selective antagonist prazosin suppressed the MEL-induced expression of IGF-I, Gαq, p-PKC, and p-ERK1/2, while the cAMP concentration was barely affected. In addition, pretreatment with Ym254890 (a Gαq inhibitor), Go9863 (a PKC inhibitor), and PD98059 (an ERK1/2 inhibitor) markedly attenuated MEL-stimulated IGF-I expression and p-ERK1/2 activity. These results indicate that Mel1c mediates monochromatic GL-stimulated IGF-I synthesis through intracellular Gαq/PKC/ERK signaling.

A Green and Blue Monochromatic Light Combination Therapy Reduces Oxidative Stress and Enhances B‐Lymphocyte Proliferation through Promoting Melatonin Secretion

“…In addition, we also observed that G→B and B→G significantly promoted the protein expression of p-PKC and p-ERK, and Mel1c may mediate a green and blue monochromatic light combination stimulated B-lymphocyte proliferation through the intracellular PKC/ERK signaling pathway. Consistent with our findings, Ning et al reported that melatonin promoted IGF-1 mRNA expression through the Mel1c-mediated PKC/ERK pathway in chick liver cells [ 52 ]. Interestingly, ERK is considered a signaling hub with many different input and output pathways with multiple crosstalks [ 53 ].…”

Physiological crosstalk between the Mel1a and Mel1c pathways modulates melatonin-mediated, monochromatic light combination-induced bursa B-lymphocyte proliferation in chickens

“…In this study, we observed that G→B and B→G signi cantly promoted the protein expression of p-PKC and p-ERK protein, and Mel1c may mediate a green and blue monochromatic light combination stimulated B-lymphocyte proliferation through the intracellular PKC/ERK signaling pathway. Consistent with our ndings, Ning et al reported that melatonin promoted IGF-1 mRNA expression through Mel1c mediated-PKC/ERK pathway in chick liver cells [48]. Interestingly, ERK is considered a signaling hub with many different input and output pathways with multiple crosstalks [49].…”

Receptor-Mediated and Receptor-Independent Actions of Melatonin in Vertebrates

“…Three types of melatonin membrane receptors have been identified: Mel1a (or MT1, ML1a, ML1, MTNR1a) and Mel1b (or MT2, ML1b, MTNR1b) receptor subtypes, which are present in humans and other mammals, while an additional melatonin receptor subtype, Mel1c (MTNR1C), has been identified in fishes, amphibians, and birds (Emet et al, 2016). Mel1a and Mel1b as GPCR bonded with Gαs to decrease cAMP, while Mel1c coupled with Gαq to activate the membrane-associated phospholipase C and protein kinase C pathways (Ning et al, 2019).…”