A thermodynamically-constrained mathematical model for the kinetics and regulation of NADPH oxidase 2 complex-mediated electron transfer and superoxide production

Clinical data has confirmed that auditory impairment may be a secondary symptom of type 2 diabetes mellitus (T2DM). However, mechanisms underlying pathologic changes that occur in the auditory system, especially in the central auditory system (CAS), remain poorly understood. In this study, Zucker diabetic fatty (ZDF) rats were used as a T2DM rat model to observe ultrastructural alterations in the auditory cortex and investigate possible mechanisms underlying CAS damage in T2DM. The auditory brainstem response (ABR) of ZDF rats was found to be markedly elevated in low (8 kHz) and high (32 kHz) frequencies. Protein expression of NADPH oxidase 2 (NOX2) and its matching subunits P22phox, P47phox, and P67phox was increased in the auditory cortex of ZDF rats. Expression of 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA oxidative damage, was also increased in the neuronal mitochondria of the auditory cortex of ZDF rats. Additionally, decreases in the mitochondrial total antioxidant capabilities (T-AOC), adenosine triphosphate (ATP) production, and mitochondrial membrane potential (MMP) were detected in the auditory cortex of ZDF rats, suggesting mitochondrial dysfunction. Transmission electron microscopy results indicated that ultrastructural damage had occurred to neurovascular units and mitochondria in the auditory cortex of ZDF rats. Furthermore, cytochrome c (Cyt c) translocation from mitochondria to cytoplasm and caspase 3-dependent apoptosis were also detected in the auditory cortex of ZDF rats. Consequently, the study demonstrated that T2DM may cause morphological damage to the CAS and that NOX2-associated mitochondrial oxidative damage and apoptosis may be partly responsible for this insult.

Download Full-text

Strain- and Substrate-Dependent Redox Mediator and Electricity Production by Pseudomonas aeruginosa

Applied and Environmental Microbiology ◽

10.1128/aem.01342-16 ◽

2016 ◽

Vol 82 (16) ◽

pp. 5026-5038 ◽

Cited By ~ 21

Author(s):

Erick M. Bosire ◽

Lars M. Blank ◽

Miriam A. Rosenbaum

Keyword(s):

Pseudomonas Aeruginosa ◽

Electron Transfer ◽

Fuel Cells ◽

Microbial Fuel Cells ◽

Pure Culture ◽

Bioelectrochemical Systems ◽

Content Type ◽

Mediated Electron Transfer ◽

Phenazine Production ◽

Model Strain

ABSTRACTPseudomonas aeruginosais an important, thriving member of microbial communities of microbial bioelectrochemical systems (BES) through the production of versatile phenazine redox mediators. Pure culture experiments with a model strain revealed synergistic interactions ofP. aeruginosawith fermenting microorganisms whereby the synergism was mediated through the shared fermentation product 2,3-butanediol. Our work here shows that the behavior and efficiency ofP. aeruginosain mediated current production is strongly dependent on the strain ofP. aeruginosa. We compared levels of phenazine production by the previously investigated model strainP. aeruginosaPA14, the alternative model strainP. aeruginosaPAO1, and the BES isolatePseudomonassp. strain KRP1 with glucose and the fermentation products 2,3-butanediol and ethanol as carbon substrates. We found significant differences in substrate-dependent phenazine production and resulting anodic current generation for the three strains, with the BES isolate KRP1 being overall the best current producer and showing the highest electrochemical activity with glucose as a substrate (19 μA cm−2with ∼150 μg ml−1phenazine carboxylic acid as a redox mediator). Surprisingly,P. aeruginosaPAO1 showed very low phenazine production and electrochemical activity under all tested conditions.IMPORTANCEMicrobial fuel cells and other microbial bioelectrochemical systems hold great promise for environmental technologies such as wastewater treatment and bioremediation. While there is much emphasis on the development of materials and devices to realize such systems, the investigation and a deeper understanding of the underlying microbiology and ecology are lagging behind. Physiological investigations focus on microorganisms exhibiting direct electron transfer in pure culture systems. Meanwhile, mediated electron transfer with natural redox compounds produced by, for example,Pseudomonas aeruginosamight enable an entire microbial community to access a solid electrode as an alternative electron acceptor. To better understand the ecological relationships between mediator producers and mediator utilizers, we here present a comparison of the phenazine-dependent electroactivities of threePseudomonasstrains. This work forms the foundation for more complex coculture investigations of mediated electron transfer in microbial fuel cells.

Download Full-text