Selenium-Containing Protein From Selenium-Enriched Spirulina platensis Attenuates High Glucose-Induced Calcification of MOVAS Cells by Inhibiting ROS-Mediated DNA Damage and Regulating MAPK and PI3K/AKT Pathways

Abstract

Hyperglycemia is the main feature of diabetes and may increase the risk of vascular calcification (VC), which is an independent predictor for cardiovascular and cerebrovascular diseases (CCD). Selenium (Se) may decrease the risk of CCD, and previous studies confirmed that Se-containing protein from Se-enriched Spirulina platensis (Se-SP) exhibited novel antioxidant potential. However, the effect of Se-SP against VC has been not investigated. Herein, the protective effect and underlying mechanism of Se-SP against high glucose-induced calcification in mouse aortic vascular smooth muscle cells (MOVAS) were explored. Inductively coupled plasma atomic emission spectroscopy (ICP-AES) results showed time-dependent uptake of Se-SP in MOVAS cells, which significantly inhibited high glucose-induced abnormal proliferation. Se-SP co-treatment also effectively attenuated high glucose-induced calcification of MOVAS cells, followed by decreased activity and expression of alkaline phosphatase (ALP). Further investigation revealed that Se-SP markedly prevented reactive oxygen species (ROS)-mediated DNA damage in glucose-treated MOVAS cells. ROS inhibition by glutathione (GSH) effectively inhibited high glucose-induced calcification, indicating that Se-SP could act as ROS inhibitor to inhibit high glucose-induced DNA damage and calcification. Moreover, Se-SP dramatically attenuated high glucose-induced dysfunction of mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase/AKT (PI3K/AKT) pathways. Se-SP after Se addition achieved enhanced potential in inhibiting high glucose-induced calcification, which validated that Se-SP as a new Se species could be a highly effective treatment for human CCD.

A review on selenium-enriched proteins: preparation, purification, identification, bioavailability, bioactivities and application

“…73 Se-Enriched Spirulina platensis protein (SSPP) could inhibit high-glucose induced calcification damage of MOVAS cells by inhibiting MAPKs and the PI3K/Akt pathway, which indicated that SSPP had potential as an effective treatment for cerebrovascular and cardiovascular diseases. 7 SSPP also could inhibit oxygen-glucose deprivation-induced apoptosis and toxicity of hippocampal neurons by regulating the opening and closing of the mitochondrial permeability transition pore, which demonstrated that SSPP had potential application as an effective preventive treatment for ischemic brain injury. 74 In addition, Zhao, et al also showed that Se-enriched Ganoderma lucidum protein could significantly protect cells from DNA oxidative damage.…”

“…Lin et al used optical and fluorescent microscopes to observe the morphology of Se-enriched Spirulina platensis protein; the results showed that Spirulina platensis protein and Spirulina platensis exhibited the same spiral shape, which was attributed to the fact that Se could not affect the morphology of the Spirulina platensis protein. 7 During the process of plant germination, plant seeds can absorb Se from the environment and convert inorganic Se into organic Se-enriched proteins. Liu et al studied the effect of different types of proteins on the accumulation order of Se during Oryza sativa L. germination, and the results indicated the total Se content in protein from low to high was gliadin < globulin < glutenin < albumin.…”

“…Lin et al used optical and fluorescent microscopes to observe the morphology of Se-enriched Spirulina platensis protein; the results showed that Spirulina platensis protein and Spirulina platensis exhibited the same spiral shape, which was attributed to the fact that Se could not affect the morphology of the Spirulina platensis protein. 7…”

“…Therefore, it is very important to extract Se-enriched proteins from Se-enriched agricultural products and evaluate their biological activities. Currently, the extraction methods of Se-enriched protein mainly include solvent extraction, 5,7 electrophoretic separation, 8 TRIzol combined with anion exchange column extraction, 4 ultrasonicassisted extraction and pulsed electric field assisted extraction. 9 Among them, the solvent extraction method is the most used method for extracting Se-enriched proteins.…”

The Role of Selenium in Atherosclerosis Development, Progression, Prevention and Treatment

“…Another molecular mechanism connecting Se status and vascular calcification was defined in experiments on high glucose-induced mouse aortic VSMCs treated with Se-rich Spirulina platensis extract. The Se-containing extract inhibited ROS production, reduced ROS-mediated DNA damage and attenuated dysfunction of MAPK and PI3K/AKT pathways, thus effectively inhibiting high glucose-induced calcification [59].…”