Vitamin D Regulation of a SOD1-to-SOD2 Antioxidative Switch to Prevent Bone Cancer

Abstract

Superoxide, a form of reactive oxygen species (ROS), is catabolized by superoxide dismutase (SOD) and contributes to carcinogenesis via the oxidative damage it inflicts on cells. The aim of this research was to analyze the potential vitamin D-mediated regulation of the antioxidative “SOD1-to-SOD2 switch” within the human MG-63 osteosarcoma model. For this study, real-time PCR analysis was performed using MG-63 cells exposed to metabolically active 1,25(OH)2D3. First, a sustained statistically significant >2-fold suppression of proliferating cell nuclear antigen (PCNA) transcripts was observed after 10 nM but not at 100 nM of 1,25(OH)2D3 treatment, suggesting a cytostatic effect. In order to assess regulators of mitochondrial oxidative phosphorylation, gene expression of COX2 and COX4l1 of the mitochondrial complex IV and antioxidative enzymes (SOD1, SOD2 and Catalase (CAT)) were monitored. For COX2 and COX4l1, no changes in gene expression were observed. However, a concomitant decrease in CAT and SOD1 mRNA, and increase in SOD2 mRNA after 24 h of 10 nM 1,25(OH)2D3 treatment were observed. A ~8-fold increase in SOD2 mRNA was apparent after 48 ours. The significant increase in SOD2 activity in the presence of vitamin D indicates an antioxidant potential and sensitization of vitamin D during osteosarcoma transformation and mitochondrial detoxification over time.

The Vitamin D, IL-6 and the eGFR Markers a Possible Way to Elucidate the Lung–Heart–Kidney Cross-Talk in COVID-19 Disease: A Foregone Conclusion

“…The EPO-mediated regulation of the central respiratory command, which involves both MEK1/2 and PI3K pathways, was seen as crucial for phrenic motor facilitation, suggestive of a spinal plasticity in respiratory motor control in prolonged poor oxygen condition. On the other hand, the vitamin K not only allows the activation of D via the hydroxylation mechanism, but also prevents cell mitochondrial dysfunction, restores oxidative phosphorylation and the aerobic glycolysis, and eventually supports the cleansing hypoxic microenvironment typical of tissues analyzed in cancers and lung and cardiovascular necrosis due to massive thromboembolism [ 3 , 4 , 5 , 41 , 43 , 44 , 45 , 46 , 47 , 48 ] ( Figure 7 ).…”

Circulating miRNAs associated with bone mineral density in healthy adult baboons

“…45 While miR-197-3p has not previously been linked to adult bone metabolism, it was identified in the downregulation of osteogenesis in human amniotic membrane-derived mesenchymal stem cells due to its suppression of SMAD2 in the TGF-β pathway during osteoblast differentiation. 46 We predict that miR-197-3p may target expression of both SOD1 and SOD2, antioxidative enzymes that respond to vitamin D levels 47 and are thought to play a critical role in the regulation of cellular senescence. 48,49 Taken together, our aBMD-associated miRNAs and their putative targets point toward the regulation of extracellular matrix proteins, apoptosis, and cell proliferation-three key components in the maintenance of bone homeostasis.…”

Circulating miRNAs associated with bone mineral density in healthy adult baboons

“…While miR-197-3p has not previously been linked to adult bone metabolism, it was identified in the downregulation of osteogenesis in human amniotic membrane-derived mesenchymal stem cells due to its suppression of SMAD2 in the TGF-β pathway during osteoblast differentiation (Avendaño-Félix et al 2019). We predict that miR-197-3p may target expression of both SOD1 and SOD2 , antioxidative enzymes that respond to vitamin D levels (Lisse 2020) and are thought to play a critical role in the regulation of cellular senescence (Zhang et al 2017; Jeong and Cho 2015).…”