Palmitate-induced lipotoxicity alters acetylation of multiple proteins in clonal β cells and human pancreatic islets.
Federica CiregiaMarco BuglianiMaurizio RonciLaura GiustiClaudia BoldriniMaria R MazzoniSandra MossutoFrancesca GranoGabriel SantosLorella MarselliGino GiannacciniAndrea UrbaniAntonio LucacchiniPiero MarchettiPublished in: Scientific reports (2017)
Type 2 diabetes is characterized by progressive β cell dysfunction, with lipotoxicity playing a possible pathogenetic role. Palmitate is often used to examine the direct effects of lipotoxicity and it may cause mitochondrial alterations by activating protein acetylation. However, it is unknown whether palmitate influences protein acetylation in β cells. We investigated lysine acetylation in mitochondrial proteins from INS-1E β cells (INS-1E) and in proteins from human pancreatic islets (HPI) after 24 h palmitate exposure. First, we confirmed that palmitate damages β cells and demonstrated that chemical inhibition of deacetylation also impairs INS-1E function and survival. Then, by 2-D gel electrophoresis, Western Blot and Liquid Chromatography-Mass Spectrometry we evaluated the effects of palmitate on protein acetylation. In mitochondrial preparations from palmitate-treated INS-1E, 32 acetylated spots were detected, with 13 proteins resulting over-acetylated. In HPI, 136 acetylated proteins were found, of which 11 were over-acetylated upon culture with palmitate. Interestingly, three proteins, glutamate dehydrogenase, mitochondrial superoxide dismutase, and SREBP-1, were over-acetylated in both INS-1E and HPI. Therefore, prolonged exposure to palmitate induces changes in β cell protein lysine acetylation and this modification could play a role in causing β cell damage. Dysregulated acetylation may be a target to counteract palmitate-induced β cell lipotoxicity.
Keyphrases
- induced apoptosis
- oxidative stress
- mass spectrometry
- type diabetes
- cell cycle arrest
- single cell
- liquid chromatography
- endothelial cells
- cell therapy
- histone deacetylase
- diabetic rats
- signaling pathway
- amino acid
- endoplasmic reticulum stress
- high glucose
- cell proliferation
- nitric oxide
- pi k akt
- insulin resistance
- adipose tissue
- small molecule
- drug induced
- induced pluripotent stem cells
- hyaluronic acid
- newly diagnosed
- simultaneous determination