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Nox4

Spider fibers in smooth muscle cells

This image submitted by Thalita Abrahao won second place at the Postdoctoral Research Symposium Thursday. Abrahao, a postdoc in Kathy Griendling’s lab, is studying vesicle trafficking in vascular smooth muscle cells.

Thalita Abrahao -- Kathy Griendling lab

Thalita Abrahao — Kathy Griendling lab

Griendling’s lab has been looking into how the enzyme Nox4 and its partner Poldip2 are involved in cell migration, and Abrahao was investigating if vascular smooth muscle cells that have less Poldip2 have changes in protein processing.

Here, green represents beta-tubulin, a protein making up fine-looking fibers (microtubules) extending through the cell. Purple represents Sec23, part of the process of vesicle trafficking and protein secretion. White indicates when beta-tubulin and Sec23 are both present. Orange marks DNA in the nucleus.

Posted on by Quinn Eastman in Heart Leave a comment

Nox4 inhibitor expands its reach to A-T

Emory dermatologist Jack Arbiser has been investigating (and recently patented) inhibitors of the enzyme Nox4 as potential anti-cancer drugs.

Nox4 has emerged as a potential therapeutic target in ataxia-telangiectasia, a rare multifaceted genetic disorder that leads to neurological problems, a weakened immune system and an increased risk of cancer. Ataxia-telangiectasia (or A-T) is caused by a defect in ATM, a sensor responsible for managing cells’ responses to DNA damage and other kinds of stress.

In a February PNAS paper, researchers at the National Cancer Institute led by William Bonner report that a Nox4 inhibitor can dial back oxidative stress and DNA damage in ataxia-telangiectasia cells, and can reduce cancer rates in a mouse model of the disease. Nox4 was activated in cells and tissue samples obtained from A-T patients.

The Nox4 inhibitor the NCI team used, fulvene-5, was originally identified by Arbiser in a 2009 Journal of Clinical Investigation paper as a possible treatment for hemangiomas, a common tumor in infants that emerges from blood vessels.

David Lambeth, an expert on the NADPH oxidase family of enzymes, and his team recently described Nox4 as an “hydrogen peroxide-generating oxygen sensor.”

 

Posted on by Quinn Eastman in Cancer Leave a comment