RT Journal Article
T1 Melatonin Improves Endoplasmic Reticulum Stress-Mediated IRE1α Pathway in Zücker Diabetic Fatty Rat
A1 Aouichat, Samira
A1 Navarro-Alarcon, Miguel
A1 Alarcón-Guijo, Pablo
A1 Salagre, Diego
A1 Ncir, Marwa
A1 Zourgui, Lazhar
A1 Agil, Ahmad
K1 Melatonin
K1 Endoplasmic reticulum stress
K1 Diabesity
K1 Kidney
K1 Caspase-3
K1 B cell lymphoma
K1 Obesity
K1 JNK Mitogen-Activated Protein Kinases
K1 Melatonina
K1 Estrés del retículo endoplásmico
K1 Riñón
K1 Caspasa 3
K1 Linfoma de células B
K1 Obesidad
K1 Proteínas quinasas JNK activadas por mitógenos
AB Obesity and diabetes are linked to an increased prevalence of kidney disease. Endoplasmic reticulum stress has recently gained growing importance in the pathogenesis of obesity and diabetes-related kidney disease. Melatonin, is an important anti-obesogenic natural bioactive compound. Previously, our research group showed that the renoprotective effect of melatonin administration was associated with restoring mitochondrial fission/fusion balance and function in a rat model of diabesity-induced kidney injury. This study was carried out to further investigate whether melatonin could suppress renal endoplasmic reticulum (ER) stress response and the downstream unfolded protein response activation under obese and diabetic conditions. Zücker diabetic fatty (ZDF) rats and lean littermates (ZL) were orally supplemented either with melatonin (10 mg/kg body weight (BW)/day) (M-ZDF and M-ZL) or vehicle (C-ZDF and C-ZL) for 17 weeks. Western blot analysis of ER stress-related markers and renal morphology were assessed. Compared to C-ZL rats, higher ER stress response associated with impaired renal morphology was observed in C-ZDF rats. Melatonin supplementation alleviated renal ER stress response in ZDF rats, by decreasing glucose-regulated protein 78 (GRP78), phosphoinositol-requiring enzyme1α (IRE1α), and ATF6 levels but had no effect on phospho-protein kinase RNA-like endoplasmic reticulum kinase (PERK) level. In addition, melatonin supplementation also restrained the ER stress-mediated apoptotic pathway, as indicated by decreased pro-apoptotic proteins phospho-c-jun amino terminal kinase (JNK), Bax, and cleaved caspase-3, as well as by upregulation of B cell lymphoma (Bcl)-2 protein. These improvements were associated with renal structural recovery. Taken together, our findings revealed that melatonin play a renoprotective role, at least in part, by suppressing ER stress and related pro-apoptotic IRE1α/JNK signaling pathway.
PB MDPI
YR 2021
FD 2021-03-08
LK http://hdl.handle.net/10668/4305
UL http://hdl.handle.net/10668/4305
LA en
NO Aouichat S, Navarro-Alarcon M, Alarcón-Guijo P, Salagre D, Ncir M, Zourgui L, et al. Melatonin Improves Endoplasmic Reticulum Stress-Mediated IRE1α Pathway in Zücker Diabetic Fatty Rat. Pharmaceuticals. 2021 Mar 8;14(3):232
DS RISalud
RD Apr 11, 2025