Chronobiological activity of cysteinyl leukotriene receptor 1 during basal and induced autophagy in the ARPE-19 retinal pigment epithelial cell line

AGING, 2021 · DOI: https://doi.org/10.18632/aging.203744 · Published: December 17, 2021

Simple Explanation

This study investigates the role of Cysteinyl leukotriene receptor 1 (CysLTR1) in autophagy regulation in a chronobiologic context using the ARPE-19 human RPE cell line. Effects of CysLTR1 inhibition on basal autophagic activity were analyzed at inactive/low and high lysosomal degradation activity with the antagonists zafirlukast (ZTK) and montelukast (MTK) at a dosage of 100 nM for 3 hours. CysLTR1 antagonization revealed a biphasic effect of CysLTR1 on autophagosome formation and lysosomal degradation that depended on the autophagic activity of cells at treatment initiation.

Study Duration

72 hours

Participants

ARPE-19 human RPE cell line

Evidence Level

Not specified

Key Findings

1
ZTK and MTK affected lysosomal degradation, but only ZTK regulated autophagosome formation.
2
Dexamethasone treatment and serum shock induced autophagy, which was repressed by CysLTR1 antagonization.
3
CysLTR1 appears to be a key player in the chronobiological regulation of basal autophagy and adaptive autophagy in RPE cells.

Research Summary

Autophagy is an important cellular mechanism for maintaining cellular homeostasis, and its impairment correlates highly with age and age-related diseases. As a newly identified autophagy modulator, CysLTR1 appears to be a key player in the chronobiological regulation of basal autophagy and adaptive autophagy in RPE cells. CysLTR1 exhibits chronobiological activity regarding autophagy regulation in polarized ARPE-19 cells by supporting or inhibiting autophagosome formation and lysosomal degradation.

Practical Implications

Understanding Disease Mechanisms

Investigating key regulatory players of autophagy helps understand the underlying mechanisms contributing to the development of multifactorial diseases.

Developing Therapeutic Strategies

Insight into complex autophagy regulation is necessary for developing strategies to ameliorate disease manifestation.

Targeting CysLTR1

This study provides data to investigate CysLTR1 as an RPE-specific or general autophagy modulator.

Study Limitations

1
Studying basal autophagy under in vitro conditions does not consider external autophagy modulators, which are present in vivo.
2
Autophagy modulation by CysLTR1 still needs to be proven in primary RPE cells and other cell types in future studies.
3
Basal autophagy in polarized ARPE-19 cells under in vitro conditions is already affected by simple cell culture handling procedures, such as medium replacement

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