Selenium-Rich Diet Induces Myocardial Structural and Functional Abnormalities by Activating Caspase-9 and Caspase-3 in Gpx-1P198L-Overexpression Transgenic Mice

Abstract

BackgroundSelenium (Se) deficiency and supplementation result in multiple effects. GPx-1 (Pro198Leu) polymorphism is associated with Se deficiency. This study aimed to observe associations between Se-deficiency/supplement and GPx-1-198Leu overexpression in myocardial injuries.Material/MethodsGPx-1P198L transgenic (Tg) mice and non-transgenic wild-type (WT) littermates were divided into Control (CON, 0.1–0.2 mg/kg), Se-deficiency (SD, <0.02 mg/kg), and Se-supplement (SS, 0.4 mg/kg) groups. Cardiac functions were observed with animal M-mode echocardiography. Se level was measured using 2,3-diamino Kenai fluorospectrophotometry. Total cardiac GPx activity was also measured. Myocardial histopathology was determined with HE and Masson’s trichrome staining. Caspase-9 and caspase-3 were measured with Western blot analysis.ResultsIn WT Se-deficient mice, cardiac GPx activity was significantly decreased, and was not elevated by overexpression of GPx-1-198Leu gene. Increased GPx activity was observed in WT Se-supplemented mice and Tg Se-supplemented mice (much more). Se deficiency as well as supplementation resulted in cardiac systolic dysfunction, which was not affected by GPx-1-198Leu gene. Se deficiency led to myocardial fibrosis and pathological changes accompanied by increased activation of caspase-9 and caspase-3. Se supplementation significantly reduced pathological changes, as well as caspase-9 and caspase-3 levels in the presence of increased myocardial fibrosis. In Se-deficient mice, GPx-1-198Leu overexpression did not significantly decrease myocardial pathological injuries and fibrosis. In Se-supplemented Tg mice, myocardial fibrosis and caspase-9 level were increased, although pathological injuries and caspase-3 were similar to that in Se-supplemented WT mice.ConclusionsSe deficiency as well as supplementation induced myocardial structural and functional abnormalities through activation of caspase-9 and caspase-3 in GPx-1P198L overexpression transgenic mice.

Effects of selenium-enriched Bacillus sp. compounds on growth performance, antioxidant status, and lipid parameters breast meat quality of Chinese Huainan partridge chicks in winter cold stress

“…Selenium (Se) is an important trace element; its beneficial effects are well documented [ 1 ] which is relatively deficient in most areas of the world. Dietary Se deficiency is considered to be a causative factor of abnormal myocardial matrix remodeling and dysfunction in the normal heart [ 2 ]. Suitable doses of Se supplementation can regulate the metabolism of nutrient substances and improve digestion, stress, and antioxidation in animals [ 3 – 5 ].…”

Keshan Disease: A Potentially Fatal Endemic Cardiomyopathy in Remote Mountains of China

“…GPx-1 activity decreases dramatically in Se deficiency and increases during Se supplementation. GPx-1 activity is also associated with GPx-1 (Pro198Leu) polymorphism ( 47 , 48 ). GPx-1 is the most prevalent of the GPx family and is found in the cytosol of all cells.…”