Manganese elevates manganese superoxide dismutase protein level through protein kinase C and protein tyrosine kinase

Abstract

Three experiments were conducted to investigate the effects of inorganic and organic Mn sources on MnSOD mRNA, protein and enzymatic activity and the possible signal pathways. The primary broiler myocardial cells were treated with MnCl2 (I) or one of organic chelates of Mn and amino acids with weak, moderate (M) or strong (S) chelation strength for 12 and 48 h. Cells were preincubated with superoxide radical anions scavenger N-acetylcysteine (NAC) or specific inhibitors for MAPKs and protein tyrosine kinase (PTK) or protein kinase C (PKC) for 30 min before treatments of I and M. The MnSOD mRNA, protein and enzymatic activity, phosphorylated MAPKs or protein kinases activations were examined. The results showed that additions of Mn increased (P < 0.05) MnSOD mRNA levels and M was more effective than I. Additions of Mn elevated (P < 0.05) MnSOD protein levels and enzymatic activities, and no differences were found among I and M. Addition of NAC did not decrease (P > 0.05) Mn-induced MnSOD mRNA and protein levels. None of the three MAPKs was phosphorylated (P > 0.05) by Mn. Additions of Mn decreased (P < 0.05) the PTK activities and increased (P < 0.05) the membrane PKC contents. Inhibitors for PTK or PKC decreased (P < 0.05) Mn-induced MnSOD protein levels. The results suggested that Mn-induced MnSOD mRNA and protein expressions be not related with NAC, and MAPK pathways might not involve in Mn-induced MnSOD mRNA expression. PKC and PTK mediated the Mn-induced MnSOD protein expression.

Concentrations of trace elements and KRAS mutations in pancreatic ductal adenocarcinoma

“…In case–control comparisons, lower concentrations of manganese and aluminum were associated with a mutated KRAS PDAC. Manganese deficiency has been linked to lower activities of manganese‐dependent superoxide dismutase (MnSOD) (Finley and Davis ; Li et al ). This enzyme reduces oxidative stress by catalyzing the conversion of superoxide to hydrogen peroxide and water (Finley and Davis ).…”

“…This enzyme reduces oxidative stress by catalyzing the conversion of superoxide to hydrogen peroxide and water (Finley and Davis ). Therefore, a possible explanation is that lower manganese levels may account for an increase in oxidative stress, favoring the occurrence and persistence of KRAS mutations (Li et al ). The association between lower concentrations of aluminum and mutated KRAS PDAC may be explained by the high correlation between aluminum and manganese (Fig.…”

“…Perhaps due to the selective advantage provided by KRAS mutations, tumor cells may be less influenced by other carcinogenic agents such as trace elements (Collisson et al ; Deramaudt and Rustgi ; Eser et al ; Porta et al ; Schlitter et al ). Decreased levels of selenium and manganese in patients with KRAS mutated tumors may be explained by their established antioxidant and gatekeeping properties, therefore suggesting a potentially important role in preventing the acquisition or persistence of KRAS mutations in PDAC (Finley and Davis ; Jackson and Combs ; Li et al ; Schrauzer et al ; Smith et al ). The previous considerations notwithstanding, it is also important to consider how KRAS mutations participate in and are themselves impacted during tumor progression.…”

Manganese enhances the expression of the manganese superoxide dismutase in cultured primary chick embryonic myocardial cells

“…However, Thongphasuk et al (1999) reported that the MnCl 2 -induced MnSOD protein expression was not inhibited by superoxide scavenger 5,5-dimethyl-1-pyrroline-1-oxide or ROS scavenger N-acetylcysteine (NAC) in human breast cancer Hs578T cells (Thongphasuk et al 1999). A recent study from our laboratory also showed that the MnSOD mRNA and protein levels of Mn-treated cells were not affected by NAC, suggesting that Mn-induced MnSOD mRNA and protein expressions or their stabilities might be independent of ROS (Li et al 2016).…”

“…The MnSOD activity was measured by the nitrite method as described by Li et al (2016). The protein concentrations in supernatants were determined by BCA Protein Assay Kit (Cat no.…”