Proteomics and phosphoproteomics study of LCMT1 overexpression and oxidative stress: overexpression of LCMT1 arrests H₂O₂-induced lose of cells viability

Abstract

Objectives: Protein phosphatase 2A (PP2A), a major serine/threonine phosphatase, is also known to be a target of ROS. The methylation of PP2A can be catalyzed by leucine carboxyl methyltransferase-1 (LCMT1), which regulates PP2A activity and substrate specificity. Methods: In the previous study, we have showed that LCMT1-dependent PP2Ac methylation arrests H 2 O 2-induced cell oxidative stress damage. To explore the possible protective mechanism, we performed iTRAQ-based comparative quantitative proteomics and phosphoproteomics studies of H 2 O 2-treated vector control and LCMT1-overexpressing cells. Results: A total of 4480 non-redundant proteins and 3801 unique phosphopeptides were identified by this means. By comparing the H 2 O 2-regulated proteins in LCMT1-overexpressing and vector control cells, we found that these differences were mainly related to protein phosphorylation, gene expression, protein maturation, the cytoskeleton and cell division. Further investigation of LCMT1 overexpression-specific regulated proteins under H 2 O 2 treatment supported the idea that LCMT1 overexpression induced ageneral dephosphorylation of proteins and indicated increased expression of non-erythrocytic hemoglobin, inactivation of MAPK3 and regulation of proteins related to Rho signal transduction, which were known to be linked to the regulation of the cytoskeleton. Discussion: These data provide proteomics and phosphoproteomics insights into the association of LCMT1-dependent PP2Ac methylation and oxidative stress and indirectly indicate that the methylation of PP2A plays an important role against oxidative stress.

Methionine-Mediated Protein Phosphatase 2A Catalytic Subunit (PP2Ac) Methylation Ameliorates the Tauopathy Induced by Manganese in Cell and Animal Models

“…We found here that PP2Ac methylation continuously activated by exogenous methionine or ABL127 significantly inhibited ROS levels, increased the GSH/GSSG ratio, and prevented the loss of cell viability and apoptosis in Mn-exposed N2a cells, and this series of changes in oxidative damage indicators may be partly attributed to the recovery of the direct control of phosphorylated tau by PP2A. These results are consistent with our previous report that the promotion of the methylation of PP2Ac by the overexpression of LCMT-1 reduced oxidative stress and protected cell viability [73].…”

The interplay of ROS and the PI3K/Akt pathway in autophagy regulation

“…One of the downstream targets of SGK1 is FoxO3, and the phosphorylation of FoxO3 leads to its retention in the cytoplasm, restraining the autophagic and apoptotic processes [104]. The mTORC2‐SGK1 pathway can maintain redox homeostasis in an Nrf2‐dependent manner facilitating the alleviation of cellular oxidative stress and supporting cell survival [105].…”

Side Effects of Coronary Stenting such as Severe Coronary Stenosis and Multiple Coronary Chronic Total Occlusions in Elderly Patients via Induced Proinflammatory and Prooxidative Stress

“…The level of inflammatory cytokine TNF- α was remarkably high in patients with acute coronary syndromes and was related to the pathogenesis of coronary atherosclerosis and coronary plaque ruptures [2]. TLR4 was related to inflammation and oxidative stress response, and TLR4 expression levels were significantly high in atherosclerotic plaques and led to the progression of atherosclerotic plaques [4, 28].…”

“…Inflammatory cytokine TNF- α directly promoted mitochondrial oxidative stress in cardiomyocytes and played a key role in oxidative stress response [1], and the high level of inflammatory cytokine TNF- α was related to the pathogenesis of coronary atherosclerosis and coronary plaque ruptures in patients with acute coronary syndromes [2]. TLR4 was related to inflammation and oxidative stress response [4], and TLR4 expression levels were significantly high in atherosclerotic plaques and led to the progression of atherosclerotic plaques [28]. ACR elevated oxidative stress in cardiomyocytes and also activated inflammatory response [5, 7].…”

“…Toll-like receptor 4 (TLR4) activation promoted inflammatory response and oxidative stress and was involved in regulating proinflammatory cytokine TNF- α through its key role in coronary atherosclerosis. TLR4 was expressed on the membranes of macrophages that promoted proinflammatory signaling and played a key role in the development of coronary atherosclerosis [3, 4]. Acrolein (ACR) promoted inflammatory response and oxidative stress response [5, 6].…”