PubMed Central (PMC3 - NLM DTD)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Targeted Overexpression of Mitochondrial Catalase Prevents Radiation-Induced Cognitive Dysfunction - Parihar, Vipan K.; Allen, Barrett D.; Tran, Katherine K.; Chmielewski, Nicole N.; Craver, Brianna M.; Martirosian, Vahan; Morganti, Josh M.; Rosi, Susanna; Vlkolinsky, Roman; Acharya, Munjal M.; Nelson, Gregory A.; Allen, Antiño R.; Limoli, Charles L.
Aims: Radiation-induced disruption of mitochondrial function can elevate oxidative stress and contribute to the metabolic perturbations believed to compromise the functionality of the central nervous system. To clarify the role of mitochondrial oxidative stress in mediating the adverse effects of radiation in the brain, we analyzed transgenic (mitochondrial catalase [MCAT]) mice that overexpress human catalase localized to the mitochondria. Results: Compared with wild-type (WT) controls, overexpression of the MCAT transgene significantly decreased cognitive dysfunction after proton irradiation. Significant improvements in behavioral performance found on novel object recognition and object recognition in place tasks were associated with a preservation of neuronal...
The Protein Oxidation Repair Enzyme Methionine Sulfoxide Reductase A Modulates Aβ Aggregation and Toxicity In Vivo - Minniti, Alicia N.; Arrazola, Macarena S.; Bravo-Zehnder, Marcela; Ramos, Francisca; Inestrosa, Nibaldo C.; Aldunate, Rebeca
Aims: To examine the role of the enzyme methionine sulfoxide reductase A-1 (MSRA-1) in amyloid-β peptide (Aβ)-peptide aggregation and toxicity in vivo, using a Caenorhabditis elegans model of the human amyloidogenic disease inclusion body myositis. Results: MSRA-1 specifically reduces oxidized methionines in proteins. Therefore, a deletion of the msra-1 gene was introduced into transgenic C. elegans worms that express the Aβ-peptide in muscle cells to prevent the reduction of oxidized methionines in proteins. In a constitutive transgenic Aβ strain that lacks MSRA-1, the number of amyloid aggregates decreases while the number of oligomeric Aβ species increases. These results correlate with...
Peroxiredoxin II Negatively Regulates Lipopolysaccharide-Induced Osteoclast Formation and Bone Loss via JNK and STAT3 - Park, Hyojung; Noh, A Long Sae Mi; Kang, Ju-Hee; Sim, Jung-Sun; Lee, Dong-Seok; Yim, Mijung
Aims: Lipopolysaccharide (LPS) is considered a prominent pathogenic factor in inflammatory bone diseases. LPS challenge contributes to the production of reactive oxygen species (ROS) in diverse inflammatory diseases. However, its mechanism remains to be clarified in bone. Thus, we investigated the critical mechanism of ROS in LPS-induced osteoclastogenesis and bone loss. Results: Antioxidant prevented LPS-induced osteoclast formation via inhibition of nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and c-Fos expression in preosteoclasts. Moreover, LPS-induced osteoclast formation via ROS was attenuated by treatment with c-Jun N-terminal protein kinase (JNK) inhibitor. Interestingly, LPS also activated signal transducer and activator of transcription...
The C-Terminal Module IV of Connective Tissue Growth Factor, Through EGFR/Nox1 Signaling, Activates the NF-κB Pathway and Proinflammatory Factors in Vascular Smooth Muscle Cells - Rodrigues-Diez, Raúl R.; Garcia-Redondo, Ana Belen; Orejudo, Macarena; Rodrigues-Diez, Raquel; Briones, Ana Maria; Bosch-Panadero, Enrique; Kery, Gyorgy; Pato, Janos; Ortiz, Alberto; Salaices, Mercedes; Egido, Jesus; Ruiz-Ortega, Marta
Aims: Connective tissue growth factor (CTGF/CCN2) is a developmental gene upregulated in pathological conditions, including cardiovascular diseases, whose product is a matricellular protein that can be degraded to biologically active fragments. Among them, the C-terminal module IV [CCN2(IV)] regulates many cellular functions, but there are no data about redox process. Therefore, we investigated whether CCN2(IV) through redox signaling regulates vascular responses. Results: CCN2(IV) increased superoxide anion (O2•−) production in murine aorta (ex vivo and in vivo) and in cultured vascular smooth muscle cells (VSMCs). In isolated murine aorta, CCN2(IV), via O2•−, increased phenylephrine-induced vascular contraction. CCN2(IV) in vivo regulated several...
Reactive Oxygen Species Deficiency Induces Autoimmunity with Type 1 Interferon Signature - Kelkka, Tiina; Kienhöfer, Deborah; Hoffmann, Markus; Linja, Marjo; Wing, Kajsa; Sareila, Outi; Hultqvist, Malin; Laajala, Essi; Chen, Zhi; Vasconcelos, Júlia; Neves, Esmeralda; Guedes, Margarida; Marques, Laura; Krönke, Gerhard; Helminen, Merja; Kainulainen, Leena; Olofsson, Peter; Jalkanen, Sirpa; Lahesmaa, Riitta; Souto-Carneiro, M. Margarida; Holmdahl, Rikard
Aims: Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the phagocyte reactive oxygen species (ROS)–producing NOX2 enzyme complex and characterized by recurrent infections associated with hyperinflammatory and autoimmune manifestations. A translational, comparative analysis of CGD patients and the corresponding ROS-deficient Ncf1m1J mutated mouse model was performed to reveal the molecular pathways operating in NOX2 complex deficient inflammation. Results: A prominent type I interferon (IFN) response signature that was accompanied by elevated autoantibody levels was identified in both mice and humans lacking functional NOX2 complex. To further underline the systemic lupus erythematosus (SLE)-related autoimmune process, we show...
CD36 Upregulation Mediated by Intranasal LV-NRF2 Treatment Mitigates Hypoxia-Induced Progression of Alzheimer's-Like Pathogenesis - Wang, Chun-Yan; Wang, Zhan-You; Xie, Jing-Wei; Cai, Jian-Hui; Wang, Tao; Xu, Ye; Wang, Xu; An, Li
Aims: There is extensive evidence that oxidative stress induces cellular dysfunction in the brain and plays a critical role in Alzheimer's disease (AD) pathogenesis. Hypoxia increases factors involved in oxidative stress injury and contributes to the onset and progression of AD. Nuclear factor erythroid 2-related factor 2 (NRF2), a major component regulating antioxidant response, is attenuated in the AD brain. Importantly, NRF2 directly regulates the alternative first exons of CD36, an important participant in oxidative and inflammatory processes. To explore the effects of hypoxia-induced deterioration of AD-like pathogenesis and investigate the correlation between hypoxia-induced NRF2 signal alterations and CD36 expression,...