Hydrogen peroxide-induced cell and tissue injury: Protective effects of Mn 2+

Recent evidence indicates that under in vitro conditions, superoxide anion and hydrogen peroxide (H 2 O 2 ) are unstable in the presence of manganese ion (Mn 2+ ). The current studies snow that in the presence of Mn 2+ , H 2 O 2 -mediated injury of endothelial cells is greatly attenuated. A source of bicarbonate ion and amino acid is required for Mn 2+ to exert its protective effects. Injury by phorbol ester-activated neutrophils is also attenuated under the same conditions. EDTA reverses the protective effects. Acute lung injury produced in vivo in rats by intratracheal instillation of glucose-glucose oxidase is almost completely blocked in rats treated with Mn 2+ and glycine. Conversely, treatment of rats with EDTA, a chelator of Mn 2+ , markedly accentuates lung injury caused by glucose-glucose oxidase. These data are consistent with the findings of others that Mn 2+ can facilitate direct oxidation of amino acids with concomitant H 2 O 2 disproportionation. This could form the basis of a new therapeutic approach against oxygen radical-mediated tissue injury.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44505/1/10753_2004_Article_BF00917314.pd

Does manganese protect cultured human skin fibroblasts against oxidative injury by UVA, dithranol and hydrogen peroxide?

Reactive oxygen species (ROS) are involved in the mechanism of photoaging and carcinogenesis. Skin is endowed with antioxidant enzymes including superoxide dismutases (SOD): cytosolic copper zinc SOD and mitochondrial manganese SOD. The aim of our study was to estimate the protective effect of manganese against oxidative injury on cultured human skin fibroblasts. Dithranol, hydrogen peroxide and UV-A radiation (375 nm) were employed as oxidative stressors. The supply of manganese chloride produced an increase in cellular content of this element up to 24 fold without concomitant elevation of MnSOD activity. Nevertheless, manganese protects cells against two of the three ROS generating systems assessed, namely hydrogen peroxyde and UV-A. This protective effect depends on the concentration of manganese in the medium, 0.1 mM and 0.2 mM protect against UVA cytotoxicity, only 0.2 mM protects against H2O2 cytotoxicity

Manganese regulation of virulence factors and oxidative stress resistance in Neisseria gonorrhoeae

Neisseria gonorrhoeae has evolved a complex and novel network of oxidative stress responses, including defence mechanisms that are dependent on manganese (Mn). We performed systematic analyses at the transcriptomic and proteomic (1D SDS-PAGE and Isotope-Coded Affinity Tag [ICAT]) levels to investigate the global expression changes that take place in a high Mn environment, which results in a Mn-dependent oxidative stress resistance phenotype. These studies revealed that there were proteins regulated at the post-transcriptional level under conditions of increased Mn concentration, including proteins involved in virulence (e.g., pilin, a key adhesin), oxidative stress defence (e.g., superoxide dismutase), cellular metabolism, protein synthesis, RNA processing and cell division. Mn regulation of inorganic pyrophosphatase (Ppa) indicated the potential involvement of phosphate metabolism in the Mn-dependent oxidative stress defence. A detailed analysis of the role of Ppa and polyphosphate kinase (Ppk) in the gonococcal oxidative stress response revealed that ppk and ppa mutant strains showed increased resistance to oxidative stress. Investigation of these mutants grown with high Mn suggests that phosphate and pyrophosphate are involved in Mn-dependent oxidative stress resistance