How Long to Read The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling

How Long Does it Take to Read The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling?

It takes the average reader 5 hours and 48 minutes to read The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling by Patrick S. Tawadros

Assuming a reading speed of 250 words per minute. Learn more

Description

Introduction. Civilian trauma remains a significant health care problem in North American society. Hemorrhagic shock and resuscitation (S/R) have been shown to prime the immune system for an exaggerated response to subsequent otherwise innocuous inflammatory stimuli such as lipopolysaccharide (LPS), resulting in multiple organ failure or death. Using a rodent model of lung injury, we previously demonstrated that antecedent S/R leads to augmented LPS-induced lung injury by way of heightened NF-kappaB nuclear translocation, resulting in increased elaboration of pro-inflammatory cytokines in alveolar macrophages. Further studies revealed that oxidative stress generated during S/R is responsible for this priming phenomenon. Our group recently identified two significant alterations to LPS signaling under oxidative stress conditions in macrophages: (1) the rapid recruitment of the LPS receptor Toll-like receptor 4 (TLR4) to membrane lipid rafts, and (2) the reprogramming of LPS signaling to a Src-dependent pathway involving phosphatidylinositol 3-kinase (PI3K).Major objective and hypothesis. The objective of this thesis is to elucidate the molecular mechanisms underlying the augmented cellular responsiveness observed in macrophages following oxidative stress. The central hypothesis is that oxidative stress regulates LPS signaling by altering the activation and assembly of TLR4 receptor signaling components through generation of the lipid ceramide.Summary of findings. In the first paper, we demonstrate that the antioxidant stilbazulenyl nitrone (STAZN), a novel second-generation azulenyl nitrone, is protective in a rodent two-hit model of lung injury involving hemorrhagic S/R and subsequent intra-tracheal LPS injection. Resultant oxidative stress and lung injury in vivo were significantly reduced by STAZN following S/R and LPS. In the second paper, we explore the mechanism underlying oxidant-induced surface up-regulation of TLR4 in macrophages. Using immunofluorescence microscopy and flow cytometry techniques, hydrogen peroxide in vitro and hemorrhagic S/R in vivo are shown to induce TLR4 translocation in macrophages in a ceramide and Src-dependent manner, and the enzyme acid sphingomyelinase (ASM) is shown to mediate ceramide generation. In the third paper, the role of ceramide in oxidant-induced macrophage priming for LPS signaling is investigated. Ceramide generation via ASM is shown to have a prominent upstream role in oxidant activation of the PI3K/Akt pathway via Src kinases in macrophages. Furthermore, oxidative stress is shown to reprogram LPS signaling to a ceramide dependent pathway.Conclusion. Together, these findings highlight the role of oxidative stress in mediating augmented cellular responsiveness following S/R, and describe the role of ceramide as a central upstream mediator of oxidant priming in macrophages. The hierarchy of signaling molecules and interactions described herein represent novel targets for modulating oxidative stress in the treatment of critical illness and organ injury.

How long is The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling?

The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling by Patrick S. Tawadros is 338 pages long, and a total of 87,204 words.

This makes it 114% the length of the average book. It also has 107% more words than the average book.

How Long Does it Take to Read The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling Aloud?

The average oral reading speed is 183 words per minute. This means it takes 7 hours and 56 minutes to read The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling aloud.

What Reading Level is The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling?

The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling is suitable for students ages 12 and up.

Note that there may be other factors that effect this rating besides length that are not factored in on this page. This may include things like complex language or sensitive topics not suitable for students of certain ages.

When deciding what to show young students always use your best judgement and consult a professional.

Where Can I Buy The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling?

The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling by Patrick S. Tawadros is sold by several retailers and bookshops. However, Read Time works with Amazon to provide an easier way to purchase books.

To buy The Role of Ceramide in Oxidant-mediated Priming of Macrophages for LPS Signaling by Patrick S. Tawadros on Amazon click the button below.