Effects of the Glucocorticoid-Mediated Mitochondrial Translocation of Glucocorticoid Receptors on Oxidative Stress and Pyroptosis in BV-2 Microglia.

Microglia are resident macrophages within the central nervous system, serving as the first responders to neuroinflammation. Glucocorticoids (GCs) may cause damage to brain tissue, but the specific mechanism remains unclear. This study was divided into two parts: a glucocorticoid receptor (GR) mitochondrial translocation intervention experiment and a mitochondrial oxidative stress inhibition experiment. BV-2 microglia were stimulated with dexamethasone (DEX) and treated with either tubastatin-A or mitoquinone (MitoQ) for 24 h. Our results showed that DEX increased the translocation of GRs to mitochondria, and this effect was accompanied by decreases in the expression of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) and mitochondrially encoded cytochrome c oxidase 3 (MT-CO3) and increases in the expression of NOD-like receptor thermal protein domain-associated protein 3 (NLRP3), caspase-1, and Gasdermin D (GSDMD). The level of mitochondrial respiratory chain complex IV (MRCC IV) and adenosine triphosphate (ATP) was decreased. An elevation in the level of mitochondrial oxidative stress and the opening of the mitochondrial permeability transition pore (mPTP) was also observed. Mechanistically, tubastatin-A significantly suppressed the mitochondrial translocation of GRs, improved the expression of mitochondrial genes, promoted the restoration of mitochondrial function, and inhibited pyroptosis. MitoQ significantly prevented mitochondrial oxidative stress, improved mitochondrial function, and reduced apoptosis and pyroptosis. Both tubastatin-A and MitoQ suppressed DEX-induced pyroptosis. This study substantiates that the increase in the mitochondrial translocation of GRs mediated by GCs exacerbates oxidative stress and pyroptosis in microglia, which indicates that the regulation of mitochondrial pathways by GCs is pathogenic to microglia.

Efficient Oxygen Evolution Reaction on Polyethylene Glycol-Modified BiVO4 Photoanode by Speeding up Proton Transfer.

The rate-determining step of the oxygen evolution reaction based on a semiconductor photoanode is the formation of the OO bond. Herein, polyethylene glycol (PEG)-modified BiVO4 photoanodes are reported, in which protons can be transferred quickly due to the high proton conductivity of PEG, resulting in the acceleration of the OO bond formation rate. These are fully demonstrated by different kinetic isotope effect values. Moreover, the open-circuit voltage (Uoc ) further illustrates that PEG passivates the surface states and surface charge recombination is reduced. The composite photoanode can achieve a maximum photocurrent density of 3.64 mA cm-2 at 1.23 V compared to 1.04 mA cm-2 for pure BiVO4 , and an onset potential of 170 mV, which is a 230 mV negative shift compared to pure BiVO4 . This work provides a new strategy to accelerate water oxidation kinetics for photoanodes by speeding up the transfer of the proton and the OO bond formation rate.

MT-CO1 expression in nine organs and tissues of different-aged MRL/lpr mice: Investigation of mitochondrial respiratory chain dysfunction at organ level in systemic lupus erythematosus pathogenesis.

Objectives: This study aims to investigate the expression patterns of mitochondrially encoded cytochrome c oxidase 1 (MT-CO1) in different organs and tissues of MRL/lpr mice aged six and 18 weeks. Materials and methods: Six-week-old female MRL/lpr mice (n=10) were considered young lupus model mice, and 18-week-old MRL/lpr mice (n=10) were considered old lupus model mice. Additionally, six-week-old (n=10) and 39-week-old (n=10) female Balb/c mice were used as the young and old controls, respectively. The messenger ribonucleic acid (mRNA) and protein expression levels of MT-CO1 in nine organs/tissues were detected via quantitative polymerase chain reaction (qPCR) and Western blot. Malondialdehyde (MDA) levels were determined with thiobarbituric acid colorimetry. The correlation coefficient of MT-CO1 mRNA levels and MDA levels in each organ/tissue at different ages was analyzed by Pearson correlation analysis. Results: The results showed that most non-immune organs/tissues (heart, lung, liver, kidneys, and intestines) showed increased MT-CO1 expression levels in younger MRL/lpr mice (p<0.05) and decreased MT-CO1 expression in older mice (p<0.05). Expression of MT-CO1 in the lymph nodes was low in younger mice but high in older mice. In other immune organs (spleen and thymus), MT-CO1 expression was low in older MRL/lpr mice. Lower mRNA expression and higher MDA levels were observed in the brains of MRL/lpr mice. However, all MRL/lpr mice showed higher MDA levels than Balb/c mice in every organ no matter younger or older MRL/lpr mice. Conclusion: Our study results suggest that lymphoid mitochondrial hyperfunction at organ level may be an important intrinsic pathogenesis in systemic lupus erythematosus activity, which may affect mitochondrial dysfunction in non-immune organs.

The expression characteristics of cytochrome C oxidase subunit I in mitochondrial of MRL/lpr lupus mice.

OBJECTIVES: We sought to analyse the expression characteristics of cytochrome C oxidase subunit I in mitochondrial of MRL/lpr lupus mice. METHODS: The whole blood of MRL/lpr lupus mice was detected for whole mitochondrial genome sequencing performed by Illumina HiSeq PE150 instrument, compared with house mouse (NC_005089.1) and screened for the maximum difference gene, MT-CO1. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to detect the mRNA and protein expression of MT-CO1 in lupus mice and control mice. The total antioxidant capacities of lupus mice and control mice were measured using the rapid 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) method. RESULTS: The mitochondrial genome sequencing showed that five mitochondrial genes had base differences and MT-CO1 was the maximum difference gene, 31 in total. Among the 31 base difference sites, 2 were missense mutations and 29 were synonymous_variant. qRT-PCR test results showed that the MT-CO1 expression in lupus mouse blood was statistically lower than that in control mice blood (t=4.333; p=0.0003). Western blot test results revealed that the expression of MT-CO1 was lower in the lupus mice compared with the control mice at the protein level. Serum total antioxidant capacity testing showed that: the serum total antioxidant capacity of lupus mice was statistically lower than that of the control mice (t=9.957; p<0.0001). CONCLUSIONS: High mutation rate and decreased expression of MT-CO1 in MRL/lpr lupus mice accompanied the decrease of antioxidant capacity, which indicated that abnormal MT-CO1 might be involved in the pathogenesis of SLE and the production of anti-dsDNA antibodies.