The Nrf2/Are Pathway Influences Intrinsic Radiosensitivity And Is Activated By Exposure To Ionizing Radiation.

Overview

This dissertation explores the radiomodulatory affects of the Nrf2/Antioxidant Response Element (Nrf2/ARE) pathway. Exposure to ionizing radiation produces a large amount of reactive oxygen species (ROS) that are a major source of DNA damage. Activation of the Nrf2/ARE pathway increases production of antioxidant enzymes that might be expected to be cytoprotective. However, initial studies with several Nrf2-inducing agents found treatment prior to ionizing radiation failed to protect lymphocytes against ...
See more details below
Other sellers (Paperback)
  • All (2) from $73.49   
  • New (2) from $73.49   
Sending request ...

More About This Book

Overview

This dissertation explores the radiomodulatory affects of the Nrf2/Antioxidant Response Element (Nrf2/ARE) pathway. Exposure to ionizing radiation produces a large amount of reactive oxygen species (ROS) that are a major source of DNA damage. Activation of the Nrf2/ARE pathway increases production of antioxidant enzymes that might be expected to be cytoprotective. However, initial studies with several Nrf2-inducing agents found treatment prior to ionizing radiation failed to protect lymphocytes against radiation-induced apoptosis and several other cell types against cell death in longer term, clonogenic assays. Nrf2-deficient mouse models were then used to test the impact of the Nrf2/ARE pathway on intrinsic cellular radiosensitivity. Mouse embryo fibroblasts with loss of Nrf2 had decreased expression of heme oxygenase 1 (HO-1) protein expression and glutathione activity, as expected, and after exposure to ionizing radiation dramatically increased ROS formation relative to wild type cells. Although no differences in initial DNA double strand breaks was observed, Nrf2 deficient cells were more radiosensitive under both aerobic and hypoxic conditions. Furthermore, Nrf2-deficient mice were sensitive to whole body irradiation with doses that were sublethal for wild type and heterozygous mice, supporting a radioprotective role of the Nrf2/ARE pathway. Studies finally focused on the ability of repeated damage to activate the Nrf2/ARE pathway over time, using a gene reporter system. No change was observed 1 to 24 hours after single dose radiation exposure, but by day 5 there was a dose-dependent increase in ARE-reporter activity above 2Gy. This correlated with expression of HO-1 in several cell lines. Similar results were obtained with five daily fractions of I to 4Gy given to cells in vitro and in spleens from irradiated mice. These data suggest that ARE-activation of cytoprotective enzymes is due to persistent oxidative stress after ionizing radiation exposure. These studies are the first to report on the impact of the Nrf2/ARE pathway on intrinsic cellular radiosensitivity and activation by ionizing radiation.
Read More Show Less

Product Details

  • ISBN-13: 9781243686985
  • Publisher: BiblioLabsII
  • Publication date: 9/7/2011
  • Pages: 114
  • Product dimensions: 7.44 (w) x 9.69 (h) x 0.24 (d)

Customer Reviews

Be the first to write a review
( 0 )
Rating Distribution

5 Star

(0)

4 Star

(0)

3 Star

(0)

2 Star

(0)

1 Star

(0)

Your Rating:

Your Name: Create a Pen Name or

Barnes & Noble.com Review Rules

Our reader reviews allow you to share your comments on titles you liked, or didn't, with others. By submitting an online review, you are representing to Barnes & Noble.com that all information contained in your review is original and accurate in all respects, and that the submission of such content by you and the posting of such content by Barnes & Noble.com does not and will not violate the rights of any third party. Please follow the rules below to help ensure that your review can be posted.

Reviews by Our Customers Under the Age of 13

We highly value and respect everyone's opinion concerning the titles we offer. However, we cannot allow persons under the age of 13 to have accounts at BN.com or to post customer reviews. Please see our Terms of Use for more details.

What to exclude from your review:

Please do not write about reviews, commentary, or information posted on the product page. If you see any errors in the information on the product page, please send us an email.

Reviews should not contain any of the following:

  • - HTML tags, profanity, obscenities, vulgarities, or comments that defame anyone
  • - Time-sensitive information such as tour dates, signings, lectures, etc.
  • - Single-word reviews. Other people will read your review to discover why you liked or didn't like the title. Be descriptive.
  • - Comments focusing on the author or that may ruin the ending for others
  • - Phone numbers, addresses, URLs
  • - Pricing and availability information or alternative ordering information
  • - Advertisements or commercial solicitation

Reminder:

  • - By submitting a review, you grant to Barnes & Noble.com and its sublicensees the royalty-free, perpetual, irrevocable right and license to use the review in accordance with the Barnes & Noble.com Terms of Use.
  • - Barnes & Noble.com reserves the right not to post any review -- particularly those that do not follow the terms and conditions of these Rules. Barnes & Noble.com also reserves the right to remove any review at any time without notice.
  • - See Terms of Use for other conditions and disclaimers.
Search for Products You'd Like to Recommend

Recommend other products that relate to your review. Just search for them below and share!

Create a Pen Name

Your Pen Name is your unique identity on BN.com. It will appear on the reviews you write and other website activities. Your Pen Name cannot be edited, changed or deleted once submitted.

 
Your Pen Name can be any combination of alphanumeric characters (plus - and _), and must be at least two characters long.

Continue Anonymously

    If you find inappropriate content, please report it to Barnes & Noble
    Why is this product inappropriate?
    Comments (optional)