Melatonin reduces the endoplasmic reticulum stress and polyubiquitinated protein accumulation induced by repeated anesthesia exposure in Caenorhabditis elegans

• Published in: Scientific reports Vol. 12; no. 1; p. 5783
• Main Authors: Shin, Hyun-Jung, Koo, Bon-Wook, Yoon, Jiwon, Kim, Heeyeon, Do, Sang-Hwan, Na, Hyo-Seok
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06-04-2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378; 692/308; 692/4017; Anesthesia; Animals; Biodegradation; Caenorhabditis elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Chemotaxis; Endoplasmic reticulum; Endoplasmic Reticulum Stress; Humanities and Social Sciences; Isoflurane; Isoflurane - adverse effects; Melatonin; Melatonin - metabolism; Melatonin - pharmacology; multidisciplinary; Nematodes; Neurotoxicity; Proteasome inhibitors; Protein folding; Proteins; Proteins - metabolism; Science; Science (multidisciplinary); Unfolded Protein Response
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-09853-y

Endoplasmic reticulum (ER) stress has been linked to anesthesia-induced neurotoxicity, but melatonin seems to play a protective role against ER stress. Synchronized
Caenorhabditis elegans
were exposed to isoflurane during the developmental period; melatonin treatment was used to evaluate its role in preventing the defective unfolded protein response (UPR) and ER-associated protein degradation (ERAD). The induced expression of
hsp-4
::GFP by isoflurane was attenuated in the isoflurane-melatonin group. Isoflurane upregulated the expression of
ire-1
, whereas melatonin did not induce
ire-1
expression in
C. elegans
even after isoflurane exposure. With luzindole treatment, the effect of melatonin on the level of
ire-1
was significantly attenuated. The reduced expression of
sel-1
,
sel-11, cdc-48.1,
and
cdc-48.2
due to isoflurane was restored by melatonin, although not up to the level of the control group. The amount of polyubiquitinated proteins was increased in the isoflurane group; however, melatonin suppressed its accumulation, which was significantly inhibited by a proteasome inhibitor, MG132. The chemotaxis index of the isoflurane-melatonin group was improved compared with the isoflurane group. Melatonin may be a potential preventive molecule against defective UPR and ERAD caused by repeated anesthesia exposure. The
ire-1
branch of the UPR and ERAD pathways can be the target of melatonin to reduce anesthesia-induced ER stress.