Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Hwang, Dae Youn; Sin, Ji Soon; Kim, Min Sun; Yim, Su Youn; Kim, Yong Kyu; Kim, Chuel Kyu; Kim, Byoung Guk; Shim, Sun Bo; Jee, Seung Wan; Lee, Su Hae; Bae, Chang Jun; Lee, Byoung Chun; Jang, Mee Kyung; Cho, Jung Sik; Chae, Kab Ryong

doi:10.3892/ijmm.21.2.169

Cited by 30 publications

(35 citation statements)

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“…Therefore, the key point in the prevention and control of AS is inhibiting the excessive apoptosis of vascular endothelial cells induced by oxygen radicals. In the present study, high concentrations of H 2 O 2 led HUVECs to undergo apoptosis, which is consistent with the findings of other studies (23,24). However, the mechanisms of apoptosis are quite complex and are controlled by various pathways and signals (25).…”

Section: Discussionsupporting

confidence: 81%

Protective effect of rhein against oxidative stress-related endothelial cell injury

et al. 2012

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Abstract. Endothelial cell injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of atherosclerosis. Therefore, phytochemicals or antioxidants that inhibit the production of ROS have clinical value for the treatment of atherosclerosis. Rhein is one of the most important active components of rhubarb (Rheum officinale), a famous traditional Chinese remedy that possesses potent antioxidant properties through undefined mechanism(s). The aim of the present study was to determine whether rhein inhibits hydrogen peroxide (H 2 O 2 )-induced injury in human umbilical vein endothelial cells (HUVECs). The oxidative injury model was established with H 2 O 2 . HUVECs were treated with different concentrations of rhein in the presence/absence of H 2 O 2 . The protective effects of rhein against the injury caused by H 2 O 2 were evaluated. HUVECs incubated with 200 µmol/l H 2 O 2 had significantly decreased cell viability, which was accompanied by cell apoptosis and upregulated Bid and caspase-3, -8 and -9 mRNA expression. Meanwhile, H 2 O 2 treatment induced a marked increase in malondialdehyde (MDA) and lactate dehydrogenase (LDH) content and decreased the nitric oxide (NO) content and nitrogen oxide synthase (NOS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity. However, pre-treatment with different rhein concentrations (2, 4, 8 and 16 µmol/l) significantly increased the viability of H 2 O 2 -injured HUVECs, decreased the MDA and LDH content, increased the NO content and NOS, SOD and GSH-PX activity in a dose-dependent manner and resulted in significant recovery from H 2 O 2 -induced cell apoptosis. In addition, the results of the qRT-PCR indicated that pre-treatment with rhein downregulates the expression of Bid and caspase-3, -8 and -9 mRNA, which plays a key role in H 2 O 2 -induced cell apoptosis. The present study shows that rhein protects endothelial cells against oxidative injury induced by H 2 O 2 , suggesting that rhein is a potential compound for the prevention and treatment of atherosclerosis. IntroductionCardiovascular disease (CVD) is the primary cause of morbidity and mortality worldwide (1). Atherosclerosis (AS), a chronic inflammatory disease that results in the deposition of oxidized lipoproteins that form fatty plaques, accounts for nearly 75% of all deaths from CVD (2,3). Vascular inflammation, especially at the endothelium cell level, has been shown to play a pivotal role in the initiation, progression and clinical complications of AS (4).Endothelial cells regulate cardiovascular health and control the elasticity of vessels. Injury of endothelial cells is the first stage of AS, and oxidative stress is regarded as a critical pathogenic factor in endothelial cell injury (5). Oxidative stress is mainly caused by the excessive accumulation of reactive oxygen species (ROS), which include hydrogen peroxide (H 2 O 2 ), superoxide anions (O 2-·) and hydroxyl radicals (·OH).ROS are continuously produced in cells as products of cellular oxidation-reductio...

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Section: Discussionsupporting

confidence: 81%

Protective effect of rhein against oxidative stress-related endothelial cell injury

et al. 2012

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“…When human SelM was overexpressed in a transgenic rat model, the animal had lower concentrations of H 2O2, higher SOD and GPX activities, and a higher neutrophil-to-lymphocyte ratio. While suggesting a role for SelM in redox balance, this result provided little insight into the specific functions of endogenous SelM (Hwang et al, 2008).…”

Section: Discussionmentioning

confidence: 68%

Molecular cloning, chromosomal localization and expression profiling of porcine selenoprotein M gene

et al. 2011

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Selenoprotein M may regulate a myriad of biological processes through its redox function. In pigs, neither the nucleotide sequence nor the amino acid sequence is known. Furthermore, patterns of tissue expression and regulation by dietary selenium (Se) have not been examined. We determined the full coding sequence (CDS) and the chromosomal location of the porcine gene, SELM, and described its expression profile in vivo under different dietary Se concentrations. The cDNA sequence of porcine SELM from the start codon to the poly(A) tail was cloned by reverse transcription PCR. The CDS contained 429 bases with a typical mammalian selenocysteine insertion sequence of form 2 (F2) located in the 3′-untranslated region. The gene was mapped to chromosome 14q21, where porcine SELM and its neighboring genes exhibited a similar organization to human homologues on chromosome 22q12.2. The expression pattern of SELM mRNA in muscle, thyroid, cerebral cortex, pituitary, testis, liver, and kidney was analyzed with real-time quantitative PCR in young male pigs fed a Se-deficient corn-soybean meal basal diet supplemented with 0.0, 0.3, or 3.0 mg Se/kg in the form of Se-rich yeast. Though the SELM mRNA abundance in each of the 7 tissues was not affected by the dietary Se concentrations, it was significantly higher in thyroid (P < 0.01) than in cerebral cortex, pituitary, testis, liver, and kidney at all of the 3 dietary Se concentrations.

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“…Furthermore, in the absence of oxidative challenge, SelM knock-down resulted in decreased cell viability and increased ROS, further demonstrating the functional importance of SelM in preventing oxidative stress. In addition, a recent study reported that overexpression of SelM in a transgenic rat model resulted in the differential regulation of antioxidants as well as the activities of antioxidant enzymes (22).…”

Section: Discussionmentioning

confidence: 99%

The Neuroprotective Functions of Selenoprotein M and its Role in Cytosolic Calcium Regulation

Reeves

Bellinger

Berry

2010

Antioxidants & Redox Signaling

138

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Selenoproteins contain the trace element selenium incorporated as selenocysteine, the 21 st amino acid. Some members of the selenoprotein family, such as the glutathione peroxidases, have well-characterized antioxidant activity, functioning in enzymatic breakdown of hydroperoxides to protect cells against oxidative stress. However, the functions of many of the 25 human selenoproteins, including the brain-enriched selenoprotein M, are unknown. We investigated selenoprotein M function by manipulating expression in murine hippocampal HT22 cells, cerebellar astrocyte C8-D1A cells, and primary neuronal cultures. Overexpression of the protein resulted in a reduction in reactive oxygen species and apoptotic cell death in response to oxidative challenge with hydrogen peroxide. In contrast, knock-down of selenoprotein M using shRNA in primary neuronal cultures caused apoptotic cell death comparable to levels resulting from addition of hydrogen peroxide. Calcium measurements with the indicator cameleon demonstrated that overexpression of selenoprotein M decreased calcium influx in response to hydrogen peroxide. Additionally, knock-down of selenoprotein M expression in cortical cultures caused higher baseline levels of cytosolic calcium than in control cells. These results suggest that selenoprotein M may have an important role in protecting against oxidative damage in the brain and may potentially function in calcium regulation. Antioxid. Redox Signal. 12, 809-818.

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Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

Cited by 30 publications

References 35 publications

Protective effect of rhein against oxidative stress-related endothelial cell injury

Protective effect of rhein against oxidative stress-related endothelial cell injury

Molecular cloning, chromosomal localization and expression profiling of porcine selenoprotein M gene

The Neuroprotective Functions of Selenoprotein M and its Role in Cytosolic Calcium Regulation

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