Investigating the interaction between Shewanella oneidensis and phenazine 1-carboxylic acid in the microbial electrochemical processes.

Many exoelectrogens utilize small redox mediators for extracellular electron transfer (EET). Notable examples include Shewanella species, which synthesize flavins, and Pseudomonas species, which produce phenazines. In natural and engineered environments, redox-active metabolites from different organisms coexist. The interaction between Shewanella oneidensis and phenazine 1-carboxylic acid (PCA, a representative phenazine compound) was investigated to demonstrate exoelectrogens utilizing metabolites secreted by other organisms as redox mediators. After 24 h in a reactor with and without added PCA (1 µM), the anodic current generated by Shewanella was 235 ± 11 and 51.7 ± 2.8 µA, respectively. Shewanella produced oxidative current approximately three times as high with medium containing PCA as with medium containing the same concentration of riboflavin. PCA also stimulated inward EET in Shewanella. The strong effect of PCA on EET was attributed to its enrichment at the biofilm/electrode interface. The PCA voltammetric peak heights with a Shewanella bioanode were 25-30 times higher than under abiotic conditions. The electrochemical properties of PCA were also altered by the transition from two-electron to single-electron electrochemistry, which suggests PCA was bound between the electrode and cell surface redox proteins. This behavior would benefit electroactive bacteria, which usually dwell in open systems where mediators are present in low concentrations. Like flavins, PCA can be immobilized under both bioanode and biocathode conditions but not under metabolically inactive conditions. Shewanella rapidly transfers electrons to PCA via its Mtr pathway. Compared with wild-type Shewanella, the PCA reduction ability was decreased in gene knockout mutants lacking Mtr pathway cytochromes, especially in the mutants with severely undermined electrode-reduction capacities. These strains also lost the ability to immobilize PCA, even under current-generating conditions.

Dexmedetomidine attenuates H2O2-induced neonatal rat cardiomyocytes apoptosis through mitochondria- and ER-medicated oxidative stress pathways.

Dexmedetomidine (DEX), an α2 adrenoceptor agonist, has sedative and analgesic properties and myocardial protective effects. However, the mechanism underlying the protective effects of DEX on the myocardium remain unclear. The present study aimed to determine whether DEX serves an important role on cardioprotection through the endoplasmic reticulum (ER)­ and mitochondria­mediated apoptosis signaling pathways. Neonatal rat cardiomyocytes (NRCMs) were cultured and divided four groups: i) Normal culture medium with 10% fetal bovine serum (control group); ii) H2O2 at 500 µM (H2O2 group); iii) DEX at 5 µM (DEX group); and iv) H2O2 plus DEX (H2O2 + DEX group). The levels of apoptosis and oxidative stress of NRCMs were investigated by ELISA, western blotting, flow cytometry and cell immunofluorescence. DEX significantly suppressed H2O2­induced apoptosis, and increased activity of caspases 3, 8 and 9 of NRCMs. DEX inhibited mitochondria­mediated oxidative stress and apoptosis, as evidenced by decreased levels of reactive oxygen species and lactic dehydrogenase, alleviated mitochondrial membrane potential depolarization, and increased Bcl­2­associated X protein/B­cell lymphoma 2 ratio. In addition, DEX decreased the activity of caspase 12, and the expression levels of glucose­regulated protein 78 kDa and serine/threonine­protein kinase/endoribonuclease IRE1, three major signaling molecules involved in the ER stress­mediated apoptosis pathway. Preventive treatment with DEX alleviates cardiomyocyte against H2O2­induced oxidative stress injury through attenuating the mitochondria­ and ER­mediated apoptosis pathways.

Propofol attenuates H2O2-induced oxidative stress and apoptosis via the mitochondria- and ER-medicated pathways in neonatal rat cardiomyocytes.

Previous studies have shown that propofol, an intravenous anesthetic commonly used in clinical practice, protects the myocardium from injury. Mitochondria- and endoplasmic reticulum (ER)-mediated oxidative stress and apoptosis are two important signaling pathways involved in myocardial injury and protection. The present study aimed to test the hypothesis that propofol could exert a cardio-protective effect via the above two pathways. Cultured neonatal rat cardiomyocytes were treated with culture medium (control group), H2O2 at 500 µM (H2O2 group), propofol at 50 µM (propofol group), and H2O2 plus propofol (H2O2 + propofol group), respectively. The oxidative stress, mitochondrial membrane potential (ΔΨm) and apoptosis of the cardiomyocytes were evaluated by a series of assays including ELISA, flow cytometry, immunofluorescence microscopy and Western blotting. Propofol significantly suppressed the H2O2-induced elevations in the activities of caspases 3, 8, 9 and 12, the ratio of Bax/Bcl-2, and cell apoptosis. Propofol also inhibited the H2O2-induced reactive oxygen species (ROS) generation, lactic dehydrogenase (LDH) release and mitochondrial transmembrane potential (ΔΨm) depolarization, and restored the H2O2-induced reductions of glutathione (GSH) and superoxide dismutase (SOD). In addition, propofol decreased the expressions of glucose-regulated protein 78 kDa (Grp78) and inositol-requiring enzyme 1α (IRE1α), two important signaling molecules in the ER-mediated apoptosis pathway. Propofol protects cardiomyocytes from H2O2-induced injury by inhibiting the mitochondria- and ER-mediated apoptosis signaling pathways.