Correlation between environmental pollutant exposure and cardiopulmonary health by serum biomarker analysis in the Swedish elderly population.

Persistent organic pollutants (POPs) affect human health through the aryl hydrocarbon receptor (AhR) pathway and are implicated in mitochondrial dysfunction. Using data from the PIVUS study, we investigated the associations of serum AhR ligand (POP)-mediated luciferase activity (AhRL), mitochondrial ATP production inhibiting substances (MIS-ATP), and those affecting reactive oxygen species (MIS-ROS) with several metabolic syndrome (MetS) and cardiopulmonary function parameters. These include insulin resistance (HOMA-IR), inflammation, oxidative stress, and cardiopulmonary variables (FVC, FEV1, LV-EF, CCA distensibility). MIS-ATP showed significant correlations with HOMA-IR and pulmonary functions, indicating its direct impact of MIS-ATP on metabolic and pulmonary health. MIS-ROS correlated with oxidative stress markers and CCA distensibility, suggesting a role in systemic inflammatory responses. This study highlights the intricate relationships between environmental pollutant mixture and cardiopulmonary health in MetS as indicated by biomarkers of POP exposure in the elderly population, suggesting POP exposure may influence MetS onset and progression through mitochondrial dysfunction.

Polystyrene Microplastics Exacerbate Systemic Inflammation in High-Fat Diet-Induced Obesity.

Microplastics (MPs) are recognized as environmental pollutants with potential implications for human health. Considering the rapid increase in obesity rates despite stable caloric intake, there is a growing concern about the link between obesity and exposure to environmental pollutants, including MPs. In this study, we conducted a comprehensive investigation utilizing in silico, in vitro, and in vivo approaches to explore the brain distribution and physiological effects of MPs. Molecular docking simulations were performed to assess the binding affinity of three plastic polymers (ethylene, propylene, and styrene) to immune cells (macrophages, CD4+, and CD8+ lymphocytes). The results revealed that styrene exhibited the highest binding affinity for macrophages. Furthermore, in vitro experiments employing fluorescence-labeled PS-MPs (fPS-MPs) of 1 µm at various concentrations demonstrated a dose-dependent binding of fPS-MPs to BV2 murine microglial cells. Subsequent oral administration of fPS-MPs to high-fat diet-induced obese mice led to the co-existence of fPS-MPs with immune cells in the blood, exacerbating impaired glucose metabolism and insulin resistance and promoting systemic inflammation. Additionally, fPS-MPs were detected throughout the brain, with increased activation of microglia in the hypothalamus. These findings suggest that PS-MPs significantly contribute to the exacerbation of systemic inflammation in high-fat diet-induced obesity by activating peripheral and central inflammatory immune cells.

Neuroprotective Effects of Aldehyde-Reducing Composition in an LPS-Induced Neuroinflammation Model of Parkinson's Disease.

Parkinson's disease (PD) is a complex neurodegenerative disease in which neuroinflammation and oxidative stress interact to contribute to pathogenesis. This study investigates the in vivo neuroprotective effects of a patented yeast extract lysate in a lipopolysaccharide (LPS)-induced neuroinflammation model. The yeast extract lysate, named aldehyde-reducing composition (ARC), exhibited potent antioxidant and anti-aldehyde activities in vitro. Oral administration of ARC at 10 or 20 units/kg/day for 3 days prior to intraperitoneal injection of LPS (10 mg/kg) effectively preserved dopaminergic neurons in the substantia nigra (SN) and striatum by preventing LPS-induced cell death. ARC also normalized the activation of microglia and astrocytes in the SN, providing further evidence for its neuroprotective properties. In the liver, ARC downregulated the LPS-induced increase in inflammatory cytokines and reversed the LPS-induced decrease in antioxidant-related genes. These findings indicate that ARC exerts potent antioxidant, anti-aldehyde, and anti-inflammatory effects in vivo, suggesting its potential as a disease-modifying agent for the prevention and treatment of neuroinflammation-related diseases, including Parkinson's disease.

A Novel Aryl Hydrocarbon Receptor Antagonist HBU651 Ameliorates Peripheral and Hypothalamic Inflammation in High-Fat Diet-Induced Obese Mice.

Obesity is a chronic peripheral inflammation condition that is strongly correlated with neurodegenerative diseases and associated with exposure to environmental chemicals. The aryl hydrocarbon receptor (AhR) is a ligand-activated nuclear receptor activated by environmental chemical, such as dioxins, and also is a regulator of inflammation through interacting with nuclear factor (NF)-κB. In this study, we evaluated the anti-obesity and anti-inflammatory activity of HBU651, a novel AhR antagonist. In BV2 microglia cells, HBU651 successfully inhibited lipopolysaccharide (LPS)-mediated nuclear localization of NF-κB and production of NF-κB-dependent proinflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6. It also restored LPS-induced mitochondrial dysfunction. While mice being fed a high-fat diet (HFD) induced peripheral and central inflammation and obesity, HBU651 alleviated HFD-induced obesity, insulin resistance, glucose intolerance, dyslipidemia, and liver enzyme activity, without hepatic and renal damage. HBU651 ameliorated the production of inflammatory cytokines and chemokines, proinflammatory Ly6chigh monocytes, and macrophage infiltration in the blood, liver, and adipose tissue. HBU651 also decreased microglial activation in the arcuate nucleus in the hypothalamus. These findings suggest that HBU651 may be a potential candidate for the treatment of obesity-related metabolic diseases.

A Small Molecule, 4-Phenylbutyric Acid, Suppresses HCV Replication via Epigenetically Induced Hepatic Hepcidin.

Hepatic hepcidin is a well-known major iron regulator and has been reported to be closely related to hepatitis C virus (HCV) replication. However, pharmacological targeting of the hepcidin in HCV replication has not been reported. A short-chain fatty acid, 4-Phenyl butyrate (4-PBA), is an acid chemical chaperone that acts as a histone deacetylase inhibitor (HDACi) to promote chromosomal histone acetylation. Here, we investigated the therapeutic effect of 4-PBA on hepcidin expression and HCV replication. We used HCV genotype 1b Huh 7.5-Con1 replicon cells and engraftment of NOD/SCID mice as in vitro and in vivo models to test the effect of 4-PBA. It was found that 4-PBA inhibited HCV replication in Huh7.5-Con1 replicon cells in a concentration- and time-dependent manner through the induction of hepcidin expression by epigenetic modification and subsequent upregulation of interferon-α signaling. HCV formed a membranous web composed of double-membrane vesicles and was utilized for RNA replication. Moreover, 4-PBA also disrupted the integrity of the membranous web and interfered with the molecular interactions critical for the assembly of the HCV replication complex. These findings suggest that 4-PBA is a key epigenetic inducer of anti-HCV hepatic hepcidin and might at least in part play a role in targeting host factors related to HCV infection as an attractive complement to current HCV therapies.

Xanthohumol ameliorates 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cellular toxicity in cultured MC3T3-E1 osteoblastic cells.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant. Xanthohumol is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The aim of the current study was to explore the role of xanthohumol in modulating the toxicity of TCDD in MC3T3-E1 osteoblastic cells. In cells treated with TCDD alone, intracellular Ca2+ concentrations, mitochondrial membrane potential disruption, reactive oxygen species production, cardiolipin peroxidation, nitric oxide release and cytochrome P450 1A1 expression were significantly increased. TCDD treatment increased the mRNA levels of extracellular signal-regulated kinase 1 and nuclear factor kappa B, and significantly decreased the level of protein kinase B (AKT) in MC3T3-E1 osteoblastic cells. However, the presence of xanthohumol alleviated the pathological effects of TCDD. In addition, xanthohumol treatment significantly increased the expression of genes associated with osteoblast differentiation (alkaline phosphatase, osteocalcin, osteoprotegerin and osterix). We conclude that xanthohumol has a beneficial influence and may antagonize TCDD toxicity in osteoblastic cells.

27-Deoxyactein prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cellular damage in MC3T3-E1 osteoblastic cells.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental contaminant that exerts its toxicity through a variety of signaling mechanisms. The present study evaluated the effects of 27-deoxyactein, one of the major constituents isolated from Cimicifuga racemosa, on TCDD-induced toxicity in osteoblastic MC3T3-E1 cells. TCDD reduced cell survival, markedly increased apoptosis, and enhanced autophagy activity. However, pre-treatment with 27-deoxyactein attenuated all TCDD-induced effects and significantly decreased intracellular calcium (Ca2+) concentrations, the collapse of the mitochondrial membrane potential (MMP), the level of reactive oxygen species (ROS), and cardiolipin peroxidation compared to the TCDD-treated controls. Additionally, TCDD-induced increases in the levels of aryl hydrocarbon receptor (AhR), cytochrome P450 1A1 (CYP1A1), and extracellular signal-regulated kinase (ERK) were significantly inhibited by 27-deoxyactein. The mRNA levels of superoxide dismutase (SOD), ERK1, and nuclear factor kappa B (NF-κB) were also effectively restored by pre-treatment with 27-deoxyactein. Furthermore, 27-deoxyactein significantly increased the expressions of genes associated with osteoblast differentiation, including alkaline phosphatase (ALP), osteocalcin, bone sialoprotein (BSP), and osterix. Taken together, the present findings demonstrate the preventive effects of 27-deoxyactein on TCDD-induced damage in osteoblasts.

Actein alleviates 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated cellular dysfunction in osteoblastic MC3T3-E1 cells.

The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is known to affect bone metabolism. We evaluated the protective effects of the triterpene glycoside actein from the herb black cohosh against TCDD-induced toxicity in MC3T3-E1 osteoblastic cells. We found that TCDD significantly reduced cell viability and increased apoptosis and autophagy in MC3T3-E1 osteoblastic cells (P < .05). In addition, TCDD treatment resulted in a significant increase in intracellular calcium concentration, mitochondrial membrane potential collapse, reactive oxygen species (ROS) production, and cardiolipin peroxidation, whereas pretreatment with actein significantly mitigated these effects (P < .05). The effects of TCDD on extracellular signal-related kinase (ERK), aryl hydrocarbon receptor, aryl hydrocarbon receptor repressor, and cytochrome P450 1A1 levels in MC3T3-E1 cells were significantly inhibited by actein. The levels of superoxide dismutase, ERK1, and nuclear factor kappa B mRNA were also effectively restored by pretreatment with actein. Furthermore, actein treatment resulted in a significant increase in alkaline phosphatase (ALP) activity and collagen content, as well as in the expression of genes associated with osteoblastic differentiation (ALP, type I collagen, osteoprotegerin, bone sialoprotein, and osterix). This study demonstrates the underlying molecular mechanisms of cytoprotection exerted by actein against TCDD-induced oxidative stress and osteoblast damage.

Exposure to tetrabromobisphenol A induces cellular dysfunction in osteoblastic MC3T3-E1 cells.

This study was undertaken to investigate the possible involvement of oxidative stress in tetrabromobisphenol A (TBBPA)-induced toxicity in osteoblastic MC3T3-E1 cells. To examine the potential effect of TBBPA on cultured osteoblastic cells, we measured cell viability, apoptosis, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, cardiolipin content, cytochrome c release, cyclophilin levels, and differentiation markers in osteoblastic MC3T3-E1 cells. TBBPA exposure for 48 h caused the apoptosis and cytotoxicity of MC3T3-E1 cells. TBBPA also induced ROS and mitochondrial superoxide production in a concentration-dependent manner. These results suggest that TBBPA induces osteoblast apoptosis and ROS production, resulting in bone diseases. Moreover, TBBPA induced cardiolipin peroxidation, cytochrome c release, and decreased ATP levels which induced apoptosis or necrosis. TBBPA decreased the differentiation markers, collagen synthesis, alkaline phosphatase activity, and calcium deposition in cells. Additionally, TBBPA decreased cyclophilin A and B releases. Taken together, these data support the notion that TBBPA inhibits osteoblast function and has detrimental effects on osteoblasts through a mechanism involving oxidative stress and mitochondrial dysfunction.

Tetrabromobisphenol A induces cellular damages in pancreatic ß-cells in vitro.

Tetrabromobisphenol A (TBBPA) is a well-known organobrominated flame retardant. TBBPA has been detected in the environment. The roles played by environmental pollutants in increasing the prevalence of metabolic syndrome are attracting increasing concern. In the present work, we investigated the effects of TBBPA on rat pancreatic ß-cells (the RIN-m5F cell line). RIN-m5F cells were incubated with different concentrations of TBBPA for 48 h, and cell viability and the extent of apoptosis were determined. We also measured the levels of inflammatory cytokines, reactive oxygen species (ROS), mitochondrial adenosine triphosphate (ATP), and cardiolipin, as well as the extent of cytochrome c release from mitochondria. TBBPA reduced the ATP level, induced cardiolipin peroxidation and cytochrome c release, and triggered apoptotic cell death. Moreover, TBBPA increased the levels of inflammatory cytokines (TNF-α and IL-1ß), nitric oxide, intracellular ROS, and mitochondrial superoxide. Together, our results indicate that TBBPA damages pancreatic ß-cells by triggering mitochondrial dysfunction and inducing apoptosis.

Perfluorooctanoic acid induces mitochondrial dysfunction in MC3T3-E1 osteoblast cells.

Perfluorooctanoic acid (PFOA), a stable organic perfluorinated compound, is an emerging persistent organic pollutant, found widely in human and wildlife populations. Recent evidence suggests that exposure to environmental toxicants can be associated with higher risks of osteoporosis and fractures. We studied the cellular toxicology of PFOA in MC3T3-E1osteoblast cells. To examine the effect of PFOA, we measured cell viability, reactive oxygen species (ROS), mitochondrial superoxide, and mitochondrial parameters including adenosine triphosphate (ATP) level, mitochondrial membrane potential (MMP), cardiolipin content, and cytochrome c release in MC3T3-E1 cells. Incubating MC3T3-E1 cells in different concentrations of PFOA for 48 h resulted in a concentration-dependent decrease in cell viability and significant inductions of ROS and mitochondrial superoxide. Moreover, PFOA induced MMP collapse, cardiolipin peroxidation, cytochrome c release, and decreased ATP levels, which in turn induced apoptosis or necrosis. When osteoblast differentiation markers were assessed, PFOA treatment caused a significant reduction in alkaline phosphatase activity, collagen synthesis, and mineralization in the cells. In summary, we found an ROS- and mitochondria-mediated pathway for the induction of cell damage by PFOA in MC3T3-E1 cells. Together, our results indicate that mitochondrial toxicity could be a plausible mechanism for the toxic effects of PFOA on osteoblast function.

Cyclophilin A regulates JNK/p38-MAPK signaling through its physical interaction with ASK1.

Cyclophilin A (CypA), a member of the immunophilin family, is predominantly localized in the cytoplasm. The peptidylprolyl isomerase (PPIase) activity of CypA has been demonstrated to be involved in diverse cellular processes, including intracellular protein trafficking, mitochondrial function, pre-mRNA processing, and maintenance of multiprotein complex stability. In this study, we have demonstrated that CypA regulates apoptosis signaling-regulating kinase 1 (ASK1) through its direct binding. ASK1 is a member of MAPK kinase kinase (MAP3K) family, and selectively activates both JNK and p38 MAPK pathways. Here, we also report that CypA negatively regulates phosphorylation of ASK1 at Ser966, and that CypA reduces ASK1 and its downstream kinases of the JNK and p38 signaling. ASK1 is known to induce caspase-3 activation and apoptosis, and CypA inhibited ASK1-mediated apoptosis by decrease in caspase-3 activity under cellular stress conditions. Overall, we conclude that CypA negatively regulates ASK1 functions by its physical interaction with ASK1.

Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM.

The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.

Overexpression of TFAM, NRF-1 and myr-AKT protects the MPP(+)-induced mitochondrial dysfunctions in neuronal cells.

BACKGROUND: Mitochondrial dysfunction is a prominent feature of neurodegenerative diseases including Parkinson's disease (PD), in which insulin signaling pathway may also be implicated because 50-80% of PD patients exhibited metabolic syndrome and insulin resistance. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its toxic metabolite, 1-methyl-4-phenyl-2,3-dihydropyridinium ion (MPP(+)), inhibit complex I in mitochondrial respiratory chain and are used widely to construct the PD models. But the precise molecular link between mitochondrial damage and insulin signaling remains unclear. METHODS AND RESULTS: Using cell-based mitochondrial activity profiling system, we systemically demonstrated that MPP(+) suppressed mitochondrial activity and mitochondrial gene expressions mediated by nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM) in SH-SY5Y cells. MPP(+) fragmented mitochondrial networks and repressed phosphorylation of AKT. Similarly, the expressions of mitochondrial genes and tyrosine hydroxylase and AKT phosphorylation were reduced in substantia nigra and striatum of MPTP-injected mice. Transient transfection of TFAM, NRF-1, or myr-AKT reversed all aspects of the MPP(+)-mediated changes. CONCLUSIONS: Mitochondrial activation by TFAM, NRF-1, and myr-AKT abrogated MPP(+)-mediated damages on mitochondria and insulin signaling, leading to recovery of nigrostriatal neurodegeneration. GENERAL SIGNIFICANCE: We suggest that TFAM, NRF-1, and AKT may be the critical points of therapeutic intervention for PD. This article is part of a Special Issue entitled Biochemistry of Mitochondria.

Preparation and application of graphene-poly (diallyldimethylammoniumchloride)-iron oxide nanoparticles buckypaper for hydrogen peroxide detection.

We have reported the preparation and characterization of a novel, freestanding, paper-like graphene (G)-poly(diallyldimethylammoniumchloride) (PDDA)-Fe3O4 nanoparticles (NPs) composite. This G-based flexible buckypaper (BP) composed of stacked G-PDDA-NP platelets exhibited excellent mechanical properties, superior electrical properties, and enzyme mimetic activity, making it potentially suitable for in electrochemical sensor applications. The negatively charged NPs were immobilized on positively charged G-PDDA through the electrostatic interaction to form nanoscale G-PDDA-NP platelets, which were further assembled by flow-directed assembly to form BP. The resulting BP has macroscopic flexibility and stiffness due to the van der Waals forces between nanoscale G-PDDA-NP platelets and interlocking-tile arrangement of the platelets. The morphology and structure of the individual G-PDDA-NP platelets and the resulting BP were analyzed by using AFM, SEM and EDX. The BP was attached to an Au or Pt electrode to construct a non-enzyme H2O2 chemical sensor. The NPs acted as a "spacer" to increase the distance between the G sheets and decrease the chances of formation of a stacked graphitic structure, thereby increasing the surface area of the G electrode. The Fe3O4 NPs immobilized and embedded in the BP have intrinsic enzyme mimetic activity like natural peroxidase. The high surface area and excellent electrical conductivity of G improved the catalytic properties of NPs. The obtained H2O2, chemical sensor exhibited prominent electrocatalytic activity towards H2O2, with a wide linear range from 10 ppm (approximately 0.3 mM) to 800 ppm (approximately 23 mM), correlation coefficient of 0.986, and a high sensitivity of 218 microA mM(-1) x cm(-2). Such low-cost G-PDDA-NP composite BPs prepared by facile methods pave way towards novel sensors with better performance.

Inhibition of inflammation and oxidative stress by Angelica dahuricae radix extract decreases apoptotic cell death and improves functional recovery after spinal cord injury.

Inflammation and oxidative stress play major roles in the pathogenesis after spinal cord injury (SCI). Here, we examined the neuroprotective effects of Angelica dahuricae radix (ADR) extract after SCI. ADR extract significantly decreased the levels of proinflammatory factors such as tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in a lipopolysaccharide (LPS)-activated microglial cell line, BV2 cells. ADR extract also significantly alleviated the level of reactive oxygen species in LPS-activated BV2 cells. To examine the neuroprotective effect of ADR extract after SCI, spinally injured rats were administered ADR extract orally at a dose of 100 mg/kg for 14 days. ADR extract treatment significantly reduced the levels of TNF-α, IL-1ß, IL-6, iNOS, and COX-2. The levels of superoxide anion (O(2·)(-)) and protein nitration were also significantly decreased by ADR extract. In addition, ADR extract inhibited p38 mitogen-activated protein kinase activation and pronerve growth factor expression in microglia after SCI. Furthermore, ADR extract significantly inhibited caspase-3 activation following apoptotic cell death of neurons and oligodendrocytes, thereby improving functional recovery after injury. Thus, our data suggest that ADR extract provides neuroprotection by alleviating inflammation and oxidative stress and can be used as an orally administered therapeutic agent for acute SCI.

Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells.

Endoplasmic reticulum (ER) and mitochondrial stress are considered causal factors that induce neurodegenerative diseases. However, the relationship between these stresses remains poorly understood. To investigate the molecular mechanism underlying crosstalk between the ER and mitochondria in neurodegeneration, we treated SH-SY5Y human neuroblastoma cells with thapsigargin and tunicamycin, two inducers of ER stress, and atrazine, a promoter of mitochondrial stress. Each pharmacological agent caused mitochondrial dysfunction, which was characterized by reduced intracellular ATP, mitochondrial membrane potential, and endogenous cellular respiration as well as an augmentation of oxidative stress. Oligonucleotide microarray analysis followed by semiquantitative RT-PCR validation assays revealed that thapsigargin and tunicamycin downregulated the expression of most mitochondria-related genes in a manner similar to that induced by atrazine. In contrast, atrazine did not alter the expression of markers of ER stress. Three-dimensional principal component analysis showed that the gene expression profile produced by atrazine treatment was distinct from that generated by ER stress. However, all three agents impaired insulin receptor substrate-1 and Akt phosphorylation in the insulin signaling pathway. Ectopic overexpression of mitochondrial transcription factor A reversed the effects of thapsigargin on mitochondria and Akt signaling. We conclude that ER stress induces neuronal cell death through common perturbation of mitochondrial function and Akt signaling.

Network clustering revealed the systemic alterations of mitochondrial protein expression.

The mitochondrial protein repertoire varies depending on the cellular state. Protein component modifications caused by mitochondrial DNA (mtDNA) depletion are related to a wide range of human diseases; however, little is known about how nuclear-encoded mitochondrial proteins (mt proteome) changes under such dysfunctional states. In this study, we investigated the systemic alterations of mtDNA-depleted (ρ(0)) mitochondria by using network analysis of gene expression data. By modularizing the quantified proteomics data into protein functional networks, systemic properties of mitochondrial dysfunction were analyzed. We discovered that up-regulated and down-regulated proteins were organized into two predominant subnetworks that exhibited distinct biological processes. The down-regulated network modules are involved in typical mitochondrial functions, while up-regulated proteins are responsible for mtDNA repair and regulation of mt protein expression and transport. Furthermore, comparisons of proteome and transcriptome data revealed that ρ(0) cells attempted to compensate for mtDNA depletion by modulating the coordinated expression/transport of mt proteins. Our results demonstrate that mt protein composition changed to remodel the functional organization of mitochondrial protein networks in response to dysfunctional cellular states. Human mt protein functional networks provide a framework for understanding how cells respond to mitochondrial dysfunctions.

Immunosensor based on the ZnO nanorod networks for the detection of H1N1 swine influenza virus.

This paper presents an immunosensor fabricated on patterned zinc oxide nanorod networks (ZNNs) for detecting the H1N1 swine influenza virus (H1N1 SIV). Nanostructured ZnO with a high isoelectric point (IEP, approximately 9.5) possesses good absorbability for proteins with low IEPs. Hydrothermally grown ZNNs were fabricated on a patterned Au electrode (0.02 cm2) through a lift-off process. To detect the H1N1 SIV, the sandwich enzyme-linked immunosorbent assay (ELISA) method was employed in the immunosensor. The immunosensor was evaluated in an acetate buffer solution containing 3,3',5,5'-tetramethylbenzidine (TMB) via cyclic voltammetry at various H1N1 SIV concentrations (1 pg/mL-5 ng/mL). The measurement results of the fabricated immunosensor showed that the reduction currents of TMB at 0.25 V logarithmically increased from 259.37 to 577.98 nA as the H1N1 SIV concentration changed from 1 pg/mL to 5 ng/mL. An H1N1 SIV immunosensor, based on the patterned ZNNs, was successfully realized for detecting 1 pg/mL-5 ng/mL H1N1 SIV concentrations, with a detection limit of 1 pg/mL for H1N1 SIV.