Study Title:

Melatonin Helps Regulate Autophagy

Study Abstract

The Syrian hamster Harderian gland exhibits sexually dimorphic porphyrin biosynthesis, wherein the female glands display an extraordinarily high concentration of porphyrins. Damage derived from this production of porphyrins, mediated by reactive oxygen species, causes the glands to develop autophagic processes, which culminate in detachment-derived cell death; these cells normally play a central role in the secretory activity of the gland. The main aim of this study was to analyze how a change in the redox state impacts autophagy. Female Syrian hamsters were treated daily with melatonin (25 μg, subcutaneously) at ZT 10 for 1-2 months (N-acetyl-5-methoxytryptamine), an endogenous antioxidant that ameliorates the deleterious effects of free radicals via a variety of mechanisms. The length of treatment affected the redox balance, the autophagy machinery, and the activation of p53 and NF-κB. One-month treatment displaces redox balance to the antioxidant side, promotes autophagy through a p53-mediated mechanism, and increases cell detachment. Meanwhile, 2-month treatment restores redox balance to the oxidant side, activates NF-κB reducing autophagy to basal levels, increases number of type II cells, and reduces number of detached cells. Our results conclude that the redox state can modulate autophagy through redox-sensitive transcriptions factors. Additionally, these findings support a hypothesis that ascribes differences in the autophagic-lysosomal pathway to epithelial cell types, thereby restricting detachment-induced autophagic cell death to epithelial cell type I.

Study Information

Vega-Naredo I, Caballero B, Sierra V, García-Macia M, de Gonzalo-Calvo D, Oliveira PJ, Rodríguez-Colunga MJ, Coto-Montes A.
Melatonin modulates autophagy through a redox-mediated action in female Syrian hamster Harderian gland controlling cell types and gland activity.
J Pineal Res.
2011 June
Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal.

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