Quantitative Analysis of the Proteome and the Succinylome in the Thyroid Tissue of High-Fat Diet-Induced Hypothyroxinemia in Rats

Abstract

Hypothyroidism is a common disease, and its molecular mechanism still needs further investigation. Lysine succinylation is found to be involved in various metabolic processes associated with hypothyroidism. We performed quantitative analysis on lysine succinylome in thyroids of rats with hypothyroxinemia, which was induced through the administration of a high-fat diet. Overall, 129 differentially expressed proteins were quantified. Downregulated proteins were enriched in the thyroid hormone synthesis and thyroid hormone signaling pathways and were mainly localized in the mitochondria. In addition, 172 lysine succinylation sites on 104 proteins were obviously changed. Decreased succinylated proteins were involved in diverse metabolic pathways and were primarily localized in mitochondria. Finally, the mitochondrial oxygen consumption rates of human normal thyroid epithelial cells were measured to further verify the role of lysine succinylation. The mitochondrial oxygen consumption rates were markedly blunted in the cells treated with palmitic acid (all p<0.05), and the changes were reversed when the cells were treated with palmitic acid and desuccinylase inhibitor together (all p<0.05). Thus, we theorize that the thyroid differentially expressed proteins and changed succinylation levels played potential roles in the mitochondria-mediated energy metabolism in the high-fat diet-induced hypothyroxinemia rat model.

The freezability of Mediterranean buffalo sperm is associated with lysine succinylation and lipid metabolism

“…A secondary antibody was purchased from Abmart: goat anti‐rabbit mouse IgG‐HRP (Abmart, Cat No M21003, ). Western blotting was performed as described previously 22 . Quantification was performed using Image J and normalized to β‐Tublin.…”

“…Western blotting was performed as described previously. 22 Quantification was performed using Image J and normalized to β-Tublin. Each loading sample of WB analysis had six mixed ejaculates, and the experiment was repeated three times.…”

“…18 Up to 70% of succinylation sites occur on mitochondrial proteins and are more frequent than on non-mitochondrial proteins. 19 There are some lysine succinylome studies related to diseases [20][21][22][23] and energy metabolism. 23 In livestock, it is found that Ksucc has a positive role in improving boar sperm motility during liquid storage at 17°C 24 and that it impedes the replacement of transition proteins in elongated spermatozoa and the disordered distribution of germ cells in the seminiferous tubules.…”

Lysine succinylation analysis reveals the effect of <i>Sirt5</i> on synovial fibroblasts in rheumatoid arthritis patients

“…Lysine is a frequent target of modification among amino acid residues in proteins. In a recent study, lysine succinylation was defined as the transfer of a succinyl group to a lysine residue, which is a newly discovered post-translational modification of proteins (4).…”

Oncometabolites drive tumorigenesis by enhancing protein acylation: from chromosomal remodelling to nonhistone modification

“…Moreover, augmented Ksucc of succinate dehydrogenase (SDH) boosts its activity and exacerbates ischaemia-reperfusion injury in SIRT5-KO mouse hearts [ 51 – 53 ]. Additionally, Ksucc plays an active role in drug resistance [ 121 ], fungal pathogenicity [ 132 ], hypothyroxinemia [ 133 ], colitis [ 134 ] and other pathological activities.…”