scholarly journals The copper chaperone CcsA coupling with superoxide dismutase SodA mediates oxidative stress response in Aspergillus fumigatus

2021 ◽  
Author(s):  
Wenlong Du ◽  
Pengfei Zhai ◽  
Shuai Liu ◽  
Yuanwei Zhang ◽  
Ling Lu
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Stress Response ◽  
Aspergillus Fumigatus ◽  
Fungal Pathogens ◽  
Oxidative Stress Response ◽  
Superoxide Dismutases ◽  
Oxygen Species ◽  
Oxidative Response

Superoxide dismutases (SODs) are important metalloenzymes that protect fungal pathogens against the toxic effects of reactive oxygen species (ROS) generated by host defense mechanisms during the infection process. The activation of Cu/Zn-SOD1 is found to be dependent on its c haperone Ccs1 ( c opper c haperone for S OD1). However, the role of Ccs1 ortholog in the human pathogen Aspergillus fumigatus and how these SODs coordinate to mediate oxidative stress response remain elusive. Here, we demonstrated that A. fumigatus CcsA, a Saccharomyces cerevisiae Ccs1 ortholog, is required for cells in response to oxidative response and the activation of Sod1. Deletion of ccsA resulted in increased ROS accumulation and enhanced sensitivity to oxidative stress due to loss of SodA activity. Molecular characterization of CcsA revealed that the conserved CXC motif is required not only for the physical interaction with SodA but also for the oxidative stress adaption. Notably, addition of Mn 2+ or overexpression of cytoplasmic Mn-SodC could rescue the defects of the ccsA or sodA deletion mutant, indicating the important role of Mn 2+ and Mn-SodC in ROS detoxification; however, deletion of CcsA-SodA complex could not affect A. fumigatus virulence. Collectively, our findings demonstrate that CcsA functions as a Cu/Zn-Sod1 chaperone that participates in the adaptation to oxidative stress in A. fumigatus and provide a better understanding of the CcsA-SodA complex-mediated oxidative stress response in filamentous fungi. IMPORTANCE Reactive oxygen species (ROS) produced by phagocytes have been reported to participate in the killing of fungal pathogens. Superoxide dismutases (SODs) are considered to be the first defense line against superoxide anions. Characterizing the regulatory mechanisms of SOD activation is important for understanding how fungi adapt to oxidative stress in hosts. Our findings demonstrated that CcsA functions as a SodA chaperone in A. fumigatus and that the conserved CXC motif within CcsA is required for its interaction with SodA and the CcsA-SodA-mediated oxidative response. These data may provide new insights into how fungal pathogens adapt to oxidative stress via the CcsA-SodA complex.

Role of actin depolymerizing factor cofilin in Aspergillus fumigatus oxidative stress response and pathogenesis

2017 ◽  
Vol 64 (3) ◽  
pp. 619-634 ◽  
Author(s):  
Xiaodong Jia ◽  
Xi Zhang ◽  
Yingsong Hu ◽  
Mandong Hu ◽  
Shuguang Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Aspergillus Fumigatus ◽  
Oxidative Stress Response ◽  
Actin Depolymerizing Factor

scholarly journals Positive feedback between ROS and cis-axis of PIASxα/p38α-SUMOylation/MK2 facilitates gastric cancer metastasis

2021 ◽  
Vol 12 (11) ◽  
Author(s):  
Qian Wang ◽  
Ci Xu ◽  
Qiang Fan ◽  
Haihua Yuan ◽  
Xin Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Gastric Cancer ◽  
Reactive Oxygen Species ◽  
Stress Response ◽  
Cancer Cells ◽  
Regulatory Mechanism ◽  
Reactive Oxygen ◽  
Oxidative Stress Response ◽  
Oxygen Species ◽  
Gastric Cancer Cells

AbstractMAPK/p38 is an important mammalian signaling cascade that responds to a variety of intracellular or extracellular stimuli, such as reactive oxygen species (ROS), and participates in numerous physiological and pathological processes. However, the biological function of p38 in different tumors, and even at different stages of the same tumor, remains elusive. To further understand the regulatory mechanism of p38 and oxidative stress in the occurrence and development of gastric cancer, we report SUMOylation as a novel post-translational modification occurring on lysine 152 of MAPK14/p38α through immunoprecipitation and series of pull-down assays in vitro and in vivo. Importantly, we determine that p38α-SUMOylation functions as an authentic sensor and accelerator of reactive oxygen species generation via interaction with and activation of MK2 in the nucleus, and the ROS accumulation, in turn, promotes the SUMOylation of p38α by stabilizing the PIASxα protein. This precise regulatory mechanism is exploited by gastric cancer cells to create an internal environment for survival and, ultimately, metastasis. This study reveals novel insights into p38α-SUMOylation and its association with the intracellular oxidative stress response, which is closely related to the processes of gastric cancer. Furthermore, the PIASxα/p38α-SUMOylation/MK2 cis-axis may serve as a desirable therapeutic target in gastric cancer as targeting PIASxα, MK2, or a specific peptide region of p38α may reconcile the aberrant oxidative stress response in gastric cancer cells.

The OxrA protein of Aspergillus fumigatus is required for the oxidative stress response and fungal pathogenesis

2021 ◽  
Author(s):  
Pengfei Zhai ◽  
Landan Shi ◽  
Guowei Zhong ◽  
Jihong Jiang ◽  
Jingwen Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Immune Response ◽  
Stress Resistance ◽  
Pathogenic Fungi ◽  
Oxidative Stress Response ◽  
Fungal Pathogenesis ◽  
Oxygen Species ◽  
Oxidative Stress Resistance

An efficient reactive oxygen species (ROS) detoxification system is vital for the survival of the pathogenic fungus Aspergillus fumigatus within the host high ROS environment of the host. Therefore, identifying and targeting factors essential for oxidative stress response is one approach to develop novel treatments for fungal infections. Oxidation resistance 1 (Oxr1) protein is essential for protection against oxidative stress in mammals, but its functions in pathogenic fungi remain unknown. The present study aimed to characterize the role of an Oxr1 homolog in A. fumigatus . The results indicated that the OxrA protein plays an important role in oxidative stress resistance by regulating the catalase function in A. fumigatus , and overexpression of catalase can rescue the phenotype associated with OxrA deficiency. Importantly, the deficiency of oxrA decreased the virulence of A. fumigatus and altered the host immune response. Using the Aspergillus -induced lung infection model, we demonstrated that the ΔoxrA mutant strain induced less tissue damage along with decreased levels of LDH and albumin release. Additionally, the ΔoxrA mutant caused inflammation at a lower degree, along with a markedly reduced influx of neutrophils to the lungs and a decreased secretion of cytokine usually associated with recruitment of neutrophils in mice. These results characterize for the role of OxrA in A. fumigatus , as a core regulator of oxidative stress resistance and fungal pathogenesis. Importance Knowledge of reactive oxygen species (ROS) detoxification in fungal pathogens is useful in the design of new antifungal drugs and could aid in the study of oxidative stress resistance mechanisms. In this study, we demonstrate that OxrA protein localize to the mitochondria and function to protect against oxidative damage. We demonstrate that OxrA contributes to oxidative stress resistance by regulating catalase function, and overexpression of catalase (CatA or CatB) can rescue the phenotype that is associated with OxrA deficiency. Remarkably, a loss of OxrA attenuated the fungal virulence in a mouse model of invasive pulmonary aspergillosis and altered the host immune response. Therefore, our finding indicates that inhibition of OxrA might be an effective approach for alleviating A. fumigatus infection. The present study is, to the best of our knowledge, a pioneer in reporting the vital role of Oxr1 protein in pathogenic fungi.

Overproduction of NOX-derived ROS in AML promotes proliferation and is associated with defective oxidative stress signaling

Blood ◽  
2013 ◽  
Vol 122 (19) ◽  
pp. 3322-3330 ◽  
Author(s):  
Paul S. Hole ◽  
Joanna Zabkiewicz ◽  
Chinmay Munje ◽  
Zarabeth Newton ◽  
Lorna Pearn ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Stress Response ◽  
Reactive Oxygen ◽  
Oxidative Stress Response ◽  
Antioxidant Defenses ◽  
Stress Signaling ◽  
Oxygen Species ◽  
Key Points ◽  
P38mapk Signaling

Key Points More than 60% of primary AML blasts constitutively produce high levels of NOX-derived reactive oxygen species (ROS), which drives AML proliferation. High ROS AMLs show depleted antioxidant defenses but evade the oxidative stress response through suppression of p38MAPK signaling.

scholarly journals ATP Activates a Reactive Oxygen Species-dependent Oxidative Stress Response and Secretion of Proinflammatory Cytokines in Macrophages

2006 ◽  
Vol 282 (5) ◽  
pp. 2871-2879 ◽  
Author(s):  
Cristiane M. Cruz ◽  
Alessandra Rinna ◽  
Henry Jay Forman ◽  
Ana L. M. Ventura ◽  
Pedro M. Persechini ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Stress Response ◽  
Proinflammatory Cytokines ◽  
Reactive Oxygen ◽  
Oxidative Stress Response ◽  
Oxygen Species

118 EXOSOME-MEDIATED OXIDATIVE STRESS RESPONSE IN BOVINE GRANULOSA CELLS

2017 ◽  
Vol 29 (1) ◽  
pp. 167
Author(s):  
M. Saeed-Zidane ◽  
D. Salilew-Wondim ◽  
L. Linden ◽  
E. Held ◽  
C. Neuhoff ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Cell Cycle ◽  
Stress Response ◽  
Granulosa Cells ◽  
Culture Medium ◽  
Oxidative Stress Response ◽  
Stress Conditions ◽  
Oxygen Species ◽  
Mitochondrial Distribution

Exosomes are nano-sized (30–100 nm) extracellular membrane vesicles released through exocytosis process in most cells and biological fluids. They contain a cargo of nucleic acids, proteins, lipids and play a vital role in cell-cell communications. Various cell types have been shown to release exosomes into extracellular space as a response to various environmental stress conditions. However, little is known about the response of granulosa cells to oxidative stress, with regard to release of exosomes that may carry mRNA and protein molecules related to cellular oxidative stress response. Here we aimed to investigate the potential release of stress elements by granulosa cells to culture media through exosomes under oxidative stress conditions. For that, bovine granulosa cells from small follicles were aspirated and cultured in DMEM/F-12 media supplemented with exosome free fetal bovine serum (Exo-FBS) and treated with 5 µM H2O2 for 40 min. Granulosa cells were collected 24 h post-treatment to quantify the expression of antioxidants (Nrf2, Keap1, SOD1, CAT1, PRDX1, HOMOX1, TXN1, and NQO1), cell proliferation (PCNA and CNND2), cell differentiation (CYP11A1 and STAR), apoptosis (Casp3), and antiapoptosis (BCL2L1) genes. Reactive oxygen species accumulation, mitochondrial distribution, cell viability, and cell cycle assays were performed in cultured granulosa cells, and the culture medium was used to isolate exosomes using ultracentrifugation procedure. The identity of exosomes was confirmed by immunoblotting of Alix and CD63 proteins, and the expression level of antioxidant was analysed in mRNA isolated from exosomes. Data from 3 independent biological replicates were statistically analysed using the 2-tailed t-test. Results showed that H2O2 treatment increased mRNA and protein level of antioxidants (Nrf2, PRDX1, and TXN1), as well as cell differentiation and apoptosis-related genes compared to untreated controls. However, granulosa cells treated with H2O2 showed lower expression of cell proliferation marker genes (PCNA and CNND2). Cells treated with H2O2 showed increases in reactive oxygen species level, inadequate mitochondrial distribution, and lower cell viability. Cell cycle assay revealed a reduction in G0/G1 proportion and increase in G2 phase in cells treated with H2O2. Higher levels of antioxidant (Nrf2, CAT1, and TXN1) transcripts were detected in exosomes isolated from media with cells under oxidative stress conditions compared to the controls. Labelling and co-transfection of exosomes from stressed cell culture medium with untreated treated recipient granulosa cells resulted in increased abundance of cellular mRNA and protein of Nrf2 and CAT1 in those cells. In conclusion, granulosa cells exposed to oxidative stress could release exosomes that carry molecules related to oxidative stress response, which can be up taken by recipient cells.

Sign in / Sign up

Export Citation Format

Share Document