Melatonin controls cell proliferation and modulates mitochondrial physiology in pancreatic stellate cells.

Autor: Estaras, Matias, Ortiz-Placin, Candido, Castillejo-Rufo, Alba, Fernandez-Bermejo, Miguel, Blanco, Gerardo, Mateos, Jose M., Vara, Daniel, Gonzalez-Cordero, Pedro L., Chamizo, Sandra, Lopez, Diego, Rojas, Adela, Jaen, Isabel, de Armas, Noelia, Salido, Gines M., Iovanna, Juan L., Santofimia-Castaño, Patricia, Gonzalez, Antonio
Zdroj: Journal of Physiology & Biochemistry; Feb2023, Vol. 79 Issue 1, p235-249, 15p
Abstrakt: We have investigated the effects of melatonin on major pathways related with cellular proliferation and energetic metabolism in pancreatic stellate cells. In the presence of melatonin (1 mM, 100 µM, 10 µM, or 1 µM), decreases in the phosphorylation of c-Jun N-terminal kinase and of p44/42 and an increase in the phosphorylation of p38 were observed. Cell viability dropped in the presence of melatonin. A rise in the phosphorylation of AMP-activated protein kinase was detected in the presence of 1 mM and 100 µM melatonin. Treatment with 1 mM melatonin decreased the phosphorylation of protein kinase B, whereas 100 µM and 10 µM melatonin increased its phosphorylation. An increase in the generation of mitochondrial reactive oxygen species and a decrease of mitochondrial membrane potential were noted following melatonin treatment. Basal and maximal respiration, ATP production by oxidative phosphorylation, spare capacity, and proton leak dropped in the presence of melatonin. The expression of complex I of the mitochondrial respiratory chain was augmented in the presence of melatonin. Conversely, in the presence of 1 mM melatonin, decreases in the expression of mitofusins 1 and 2 were detected. The glycolysis and the glycolytic capacity were diminished in cells treated with 1 mM or 100 µM melatonin. Increases in the expression of phosphofructokinase-1 and lactate dehydrogenase were noted in cells incubated with 100 µM, 10 µM, or 1 µM melatonin. The expression of glucose transporter 1 was increased in cells incubated with 10 µM or 1 µM melatonin. Conversely, 1 mM melatonin decreased the expression of all three proteins. Our results suggest that melatonin, at pharmacological concentrations, might modulate mitochondrial physiology and energy metabolism in addition to major pathways involved in pancreatic stellate cell proliferation. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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