Effects of melatonin on autophagic processes in the liver of diabetic rats
2015
Authors:
Petrović, AnjaBogojević, Desanka
Ivanović-Matić, Svetlana
Martinović, Vesna
Korać, Aleksandra
Jovanović-Stojanov, Sofija
Stevanović, Jelena
Poznanović, Goran
Grigorov, Ilijana
Contributors
Korać, BatoStančić, Ana
Document Type:
Conference object (Published version)
,
© 2015 by the Serbian Society for Mitochondrial and Free-Radical Physiology
Metadata
Show full item recordAbstract:
Autophagy is a cellular process that involves lysosomal degradation and recycling of intracellular
organelles and proteins. By removing damaged and dysfunctional cellular components in order to
maintain energy homeostasis during cellular stress, autophagy can serve as a cytoprotective
mechanism. Also, it could lead to cell death if it‟s overactive or defective. Molecular mechanisms
responsible for the two faces of autophagy are still partially known. Therefore, for the development of
therapy based on autophagy modulation, it‟s necessary to fully define these processes. This study
investigated the role of oxidative stress on autophagic processes in the liver of diabetic rats and effects
of melatonin, as an antioxidant, on autophagy initiation/modulation. The liver, as one of the main
target organs of insulin, takes an important role in regulation of glucose homeostasis. In diabetes,
hypoinsulinemia followed by hyperglycemia increases mitochondrial proton gradient within the cells.
In this state organelles become the source of reactive oxidative species leading to macromolecule
damage which may cause necrotic, apoptotic or autophagic cell death. In the liver of diabetic rats
obtained four weeks after diabetes induction with streptozotocin (65 mg/kg, i.p.), light and electron
transmission microscopy showed significant changes in the structure of the cells and a large number of
necrotic cells. By using Western blot, immunoprecipitation and confocal microscopy analyses,
autophagy in diabetic liver was confirmed by increased expression of proteins required for
autophagosome formation, LC3B and Beclin1, and by the presence of Beclin1 interactions with its
activator HMGB1. In the state of oxidative stress HMGB1 is relocated from the nucleus to the
cytoplasm. Continuous melatonin treatment of diabetic rats (2mg/kg/daily, i.p.) leads to significant
reduction of liver damage, presumably through elevated mitochondrial autophagy. Melatonin
additionally contributes to elevated expression of LC3B and Beclin1, HMGB1-Beclin1 interactions
and autophagosome formation. Thus, it seems that melatonin protects the liver from diabetes induced
damage by favoring autophagy as a protective mechanism.
Funding / projects:
- Signaling molecules in diabetes: search for potential targets in intrinsic pathways for prediction and intervention in diabetes (RS-MESTD-Basic Research (BR or ON)-173020)
In:
- Korać B, Stančić A, editors. Book of Abstracts: Third Congress Redox Medicine: Reactive Species Signaling, Analytical Methods, Phytopharmacy, Molecular Mechanisms of Disease - SSMFRP-2015; 2015 Sep 25-26; Belgrade, Serbia. Belgrade: Serbian Society for Mitochondrial and Free-Radical Physiology; 2015. p. 33.