Reactive oxygen species induce reversible PECAM-1 tyrosine phosphorylation and SHP-2 binding

2003 ◽  
Vol 285 (6) ◽  
pp. H2336-H2344 ◽  
Author(s):  
Matthias Maas ◽  
Ronggang Wang ◽  
Cathy Paddock ◽  
Srigiridhar Kotamraju ◽  
Balaraman Kalyanaraman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Phosphatase ◽  
Reactive Oxygen ◽  
Protein Tyrosine Phosphatases ◽  
Sh2 Domain ◽  
Oxygen Species ◽  
Protein Tyrosine ◽  
High Concentrations

Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) functions to control the activation and survival of the cells on which it is expressed. Many of the regulatory functions of PECAM-1 are dependent on its tyrosine phosphorylation and subsequent recruitment of the Src homology (SH2) domain containing protein tyrosine phosphatase SHP-2. The recent demonstration that PECAM-1 tyrosine phosphorylation occurs in cells exposed to the reactive oxygen species hydrogen peroxide (H2O2) suggested that this form of oxidative stress may also support PECAM-1/SHP-2 complex formation. In the present study, we show that PECAM-1 tyrosine phosphorylation in response to exposure of cells to H2O2 is reversible, involves a shift in the balance between kinase and phosphatase activities, and supports binding of SHP-2 and recruitment of this phosphatase to cell-cell borders. We speculate, however, that the unique ability of H2O2 to reversibly oxidize the reactive site cysteine residues of protein tyrosine phosphatases may result in transient inactivation of the SHP-2 that is bound to PECAM-1 under these conditions. Finally, we provide evidence that PECAM-1 tyrosine phosphorylation and SHP-2 binding in endothelial cells requires exposure to an “oxidative burst” of H2O2, but that exposure of these cells to sufficiently high concentrations of H2O2 for a sufficiently long period of time abrogates binding of SHP-2 to tyrosine-phosphorylated PECAM-1. These findings support a role for PECAM-1 as a sensor of oxidative stress, perhaps most importantly during the process of inflammation.

scholarly journals Reactive oxygen species as essential mediators of cell adhesion

2003 ◽  
Vol 161 (5) ◽  
pp. 933-944 ◽  
Author(s):  
Paola Chiarugi ◽  
Giovambattista Pani ◽  
Elisa Giannoni ◽  
Letizia Taddei ◽  
Renata Colavitti ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Adhesion ◽  
Tyrosine Phosphatase ◽  
Adhesion Formation ◽  
Reactive Oxygen ◽  
Protein Tyrosine Phosphatases ◽  
Redox Signaling ◽  
Growth Factor Signaling ◽  
Oxygen Species ◽  
Protein Tyrosine

Signal transduction by reactive oxygen species (ROS; “redox signaling”) has recently come into focus in cellular biology studies. The signaling properties of ROS are largely due to the reversible oxidation of redox-sensitive target proteins, and especially of protein tyrosine phosphatases, whose activity is dependent on the redox state of a low pKa active site cysteine. A variety of mitogenic signals, including those released by receptor tyrosine kinase (RTKs) ligands and oncogenic H-Ras, involve as a critical downstream event the intracellular generation of ROS. Signaling by integrins is also essential for the growth of most cell types and is constantly integrated with growth factor signaling. We provide here evidence that intracellular ROS are generated after integrin engagement and that these oxidant intermediates are necessary for integrin signaling during fibroblast adhesion and spreading. Moreover, we propose a synergistic action of integrins and RTKs for redox signaling. Integrin-induced ROS are required to oxidize/inhibit the low molecular weight phosphotyrosine phosphatase, thereby preventing the enzyme from dephosphorylating and inactivating FAK. Accordingly, FAK phosphorylation and other downstream events, including MAPK phosphorylation, Src phosphorylation, focal adhesion formation, and cell spreading, are all significantly attenuated by inhibition of redox signaling. Hence, we have outlined a redox circuitry whereby, upon cell adhesion, oxidative inhibition of a protein tyrosine phosphatase promotes the phosphorylation/activation and the downstream signaling of FAK and, as a final event, cell adhesion and spreading onto fibronectin.

scholarly journals Impacts of Oxidative Stress and Antioxidants on Semen Functions

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Amrit Kaur Bansal ◽  
G. S. Bilaspuri
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Sperm Quality ◽  
Reactive Oxygen ◽  
The Body ◽  
Atp Depletion ◽  
Contributory Factor ◽  
Ros Generation ◽  
Oxygen Species ◽  
High Concentrations

Oxidative stress (OS) has been considered a major contributory factor to the infertility. Oxidative stress is the result of imbalance between the reactive oxygen species (ROS) and antioxidants in the body which can lead to sperm damage, deformity, and eventually male infertility. Although high concentrations of the ROS cause sperm pathology (ATP depletion) leading to insufficient axonemal phosphorylation, lipid peroxidation, and loss of motility and viability but, many evidences demonstrate that low and controlled concentrations of these ROS play an important role in sperm physiological processes such as capacitation, acrosome reaction, and signaling processes to ensure fertilization. The supplementation of a cryopreservation extender with antioxidant has been shown to provide a cryoprotective effect on mammalian sperm quality. This paper reviews the impacts of oxidative stress and reactive oxygen species on spermatozoa functions, causes of ROS generation, and antioxidative strategies to reduce OS. In addition, we also highlight the emerging concept of utilizing OS as a tool of contraception.

scholarly journals The effect of acrylamide on sperm oxidative stress, total antioxidant levels, tyrosine phosphorylation, and carboxymethyl-lysine expression: A laboratory study

2021 ◽  
Author(s):  
Mojdeh Hosseinpoor Kashani ◽  
Mina Ramezani ◽  
Zeinab Piravar
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Tyrosine Phosphorylation ◽  
Laboratory Study ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Total Antioxidant ◽  
Carboxymethyl Lysine

Background: Acrylamide (AA) is a reactive molecule produced during food processing at temperatures above 120°C. Objective: To evaluate the impact of different concentrations of AA on human sperm parameters, oxidative stress and total antioxidant capacity (TAC). Materials and Methods: In this laboratory study, semen samples were obtained from healthy donors referred to the Taleghani Hospital, Tehran, Iran between June and July 2019. Samples were divided into four groups (n = 10/each): one control and three treatment groups (0.5, 1, and 2 mM of AA). After 2 hr of exposure to AA, the superoxide dismutase and malondialdehyde levels were measured based on colorimetric methods. The TAC was determined by the ferric-reducing antioxidant power assay. Flow cytometry was performed to measure the intracellular reactive oxygen species generation. Also, immunohistochemistry was done to determine the effect of AA on tyrosine phosphorylation and carboxymethyl-lysine expression. Results: Results of the study demonstrated that the motility and viability of spermatozoa were significantly decreased after AA exposure (p < 0.001). This decrease was also seen in the TAC and superoxide dismutase activity as well as in the phosphotyrosine percentage compared with the control (p < 0.01). However, the carboxymethyllysine and prooxidant activity including reactive oxygen species generation and lipid peroxidation level increased (p < 0.001). Conclusion: Overall, the results confirmed the detrimental effect of AA on human spermatozoa which may be due to oxidative stress and decreased total antioxidant levels. AA may reduce fertility by reducing sperm capacitation and motility. Key words: Acrylamide, Oxidative stress, Antioxidant, Spermatozoa, Infertility.

Modeling Peroxidase-Oxidase Interactions

2011 ◽  
Author(s):  
W. M. Schaffer ◽  
T. V. Bronnikova
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Low Concentrations ◽  
Wide Range ◽  
Regulatory Capacity ◽  
Episodic Nature ◽  
High Concentrations

Reactive oxygen species (ROS) and peroxidase-oxidase (PO) reactions are Janus-faced contributors to cellular metabolism. At low concentrations, reactive oxygen species serve as signaling molecules; at high concentrations, as destroyers of proteins, lipids and DNA. Correspondingly, PO reactions are both sources and consumers of ROS. In the present paper, we study a well-tested model of the PO reaction based on horseradish peroxidase chemistry. Our principal predictions are these: 1. Under hypoxia, the PO reaction can emit pulses of hydrogen peroxide at apparently arbitrarily long intervals. 2. For a wide range of input rates, continuing infusions of ROS are transduced into bounded dynamics. 3. The response to ROS input is hysteretic. 4. With sufficient input, regulatory capacity is exceeded and hydrogen peroxide, but not superoxide, accumulates. These results are discussed with regard to the episodic nature of neurodevelopmental and neurodegenerative diseases that have been linked to oxidative stress and to downstream interactions that may result in positive feedback and pathology of increasing severity.

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