Upregulation of UCP2 Expression Protects against LPS-Induced Oxidative Stress and Apoptosis in Cardiomyocytes

Abstract

Uncoupling protein 2 (UCP2) has a cardioprotective role under septic conditions, but the underlying mechanism remains unclear. This study aimed at investigating the effects of UCP2 on the oxidative stress and apoptosis of cardiomyocytes induced by lipopolysaccharide (LPS). First, LPS increased UCP2 expression in cardiomyocytes in a time-dependent manner. LPS increased the production of lactate dehydrogenase (LDH), reactive oxygen species (ROS), and malondialdehyde (MDA) and decreased the level of superoxide dismutase (SOD). However, UCP2 knockdown increased the LPS-induced cardiac injury and oxidative stress. In addition, LPS damaged the mitochondrial ultrastructure and led to the disruption of mitochondrial membrane potential (MMP), as well as the release of mitochondrial cytochrome c. UCP2 knockdown aggravated mitochondrial injury and the release of mitochondrial cytochrome c. LPS increased the protein levels of Bax and cleaved-caspase-3, decreased the protein level of Bcl-2, and upregulated the protein level of mitogen-activated protein kinase. However, upon UCP2 knockdown, the protein levels of Bax and cleaved-caspase-3 increased even further, and the protein level of Bcl-2 was further decreased. The protein level of phosphorylated p38 was also further enhanced. Thus, UCP2 protects against LPS-induced oxidative stress and apoptosis in cardiomyocytes.

Deletion of Mitochondrial Uncoupling Protein 2 Exacerbates Mitochondrial Damage in Mice Subjected to Cerebral Ischemia and Reperfusion Injury under both Normo- and Hyperglycemic Conditions

“…The impact of UCP2 on mitochondrial morphology of the brain tissue after cerebral ischemia and reperfusion has not been reported. Several studies have demonstrated that silencing UCP2 by small interference RNA resulted in more severe mitochondrial swelling, vacuolization and loss of matrix content in cardiomyocytic H9C2 cells and astrocytes compared with control cells challenged with sepsis [47,52,53]. These results support our finding that UCP2 plays an important role in maintaining mitochondrial dynamic and morphological integrity in the brain.…”

The Chemistry of Reactive Oxygen Species (ROS) Revisited: Outlining Their Role in Biological Macromolecules (DNA, Lipids and Proteins) and Induced Pathologies

“…Inside cell and mitochondria, the harmful effects of ROS include structural changes in DNA and RNA, peroxidation of membrane phospholipids (composed of polyunsaturated fatty acids) and oxidation of cellular proteins that perform numerous functions inside the cell. It is therefore important to keep ROS levels at physiological values, preventing them from increasing and triggering the expression of the mitochondrial protein UCP2 on its inner membrane [ 61 ]. The uncoupling protein (UCP) family acts as a proton channel or transporter, housed in the mitochondrial inner membrane.…”

Early life thermal stress modulates hepatic expression of thermotolerance related genes and physiological responses in two rabbit breeds

“…However, at 13 weeks of age (Figure 4(G)) thermally conditioned rabbit in both breeds had overexpressed hepatic UCP2 compared to their control groups indicating a protective function of this overexpression and improve thermotolerance acquisition resulted from thermal conditioning at early life. The substantial role of UCP2 is to monitor mitochondria-derived ROS production (Sreedhar and Zhao 2017) and the upregulation of UCP2 may reduce ROS production due to its antioxidative protective effects (Huang et al 2019;Migliaccio et al 2019). Besides, UCP2 overexpression may enhance cytoprotection by alleviating oxidative stress (Mattiasson et al 2003) and attenuating superoxide production to protect hepatic damage in mice due to oxidative stress (Zhang et al 2003).…”