Featured Research

from universities, journals, and other organizations

Understanding Cell Death May Bring New Life To Kidney Treatment

Date:
April 15, 2006
Source:
Medical College of Georgia
Summary:
Finding how two proteins conspire to get kidney cells to self-destruct when oxygen supplies are low may one day improve dismal mortality rates for ischemic renal failure, researchers say.

Dr. Zheng Dong, cell biologist at the Medical College of Georgia. (Phil Jones photo)

Finding how two proteins conspire to get kidney cells to self-destruct when oxygen supplies are low may one day improve dismal mortality rates for ischemic renal failure, researchers say.

Dehydration, low blood pressure, septic shock, trauma or removing a kidney for transplantation can temporarily halt or reduce blood and oxygen supplies, says Dr. Zheng Dong, cell biologist at the Medical College of Georgia.

Ischemia leads to cell suicide or apoptosis, particularly in the energy-consuming tubular cells of the kidneys, he says. Fifty percent mortality rates from resulting ischemic renal failure haven’t changed in nearly as many years, Dr. Dong says.

Tubular cells – which have the daunting daily task of reabsorbing nearly 50 gallons of usuable fluid volume, including salt and glucose the kidneys filter from the blood every 24 hours – are particularly vulnerable to apoptosis and injury, Dr. Dong says.

“They are highly energy-dependent,” he says. “That is why when you shut off the blood supply, these cells are quickly, irreversibly damaged and they die.” Tubular cell injury and death is why kidneys are so vulnerable, for example in critically ill patients.

It’s in this oxygen-deprived environment that two proteins, Bid and Bax – each a known killer in its own right – are activated and may partner to induce cell death. The killing proteins are pervasive, particularly in the kidneys, says Dr. Dong, who recently received a $1 million grant from the National Institute of Diabetes & Digestive & Kidney Diseases, to better understand their role in cell death during ischemic renal failure.

In both cell culture and animal models of ischemic renal injury, Dr. Dong and his colleagues have found Bid is cleaved or cut, releasing active fragments. Although he still doesn’t know what cuts Bid, that act enables the protein to move from its usual place in the outer region of the cell to inside its powerhouses or mitochondria.

Cleaving results in what Dr. Dong calls truncated Bid or “tBid,” which may interact with Bax and produce a conformational change. “Now Bax can move,” says Dr. Dong, and it also heads straight for the mitochondria, which normally feed and oxygenate cells. Once inside, Bax bits re-collect, forming a complex capable of making a hole in the mitochondria and enabling molecules, such as cytochrome C, a major enabler of cell respiration, to escape. “This process as we have shown probably is mediated by Bax, and now we have found that Bid can be a critical trigger of Bax,” Dr. Dong says.

A Bid knockout mouse model, developed at the University of Pittsburgh, helps illustrate the synergism. Without Bid, there is less apoptosis while kidney function and survival rates significantly improve. Also, interestingly, without Bid, cell regeneration that helps the kidney recover from ischemia is slower, he notes.

The kidney normally has some capacity to regenerate, with surviving cells quickly stretching to cover holes left by dead cells and later dividing to form more cells for tissue repair. “Within a couple of hours, neighboring cells will stretch to cover the wound, to take up the work of the dying cells,” Dr. Dong says.

Unfortunately, while some kidney cells are working hard to make up the loss, Bid and Bax continue to trigger apoptosis and eventually the kidney fails, he says.

One goal is finding the protease that cleaves Bid – he doesn’t think it’s Bax – and following the ensuing cascade to better understand the process so it can be manipulated to stop needless cell death or, in the case of cancer, enhance self-destruction.

In related research, Dr. Dong’s lab is studying kidney damage caused by the common chemotherapeutic agent, Cisplatin, used for testicular, ovarian and small cell lung cancer, head and neck tumors and more. Renal function is closely monitored while on therapy because of the drug’s known side effects in the kidney.

“We want to see how the drug can kill kidney cells and if we can find a protective mechanism to prevent kidney cell death without stopping cancer cell death,” says Dr. Dong. He thinks the answer may be in the differences between healthy and cancerous cells.


Story Source:

The above story is based on materials provided by Medical College of Georgia. Note: Materials may be edited for content and length.


Cite This Page:

Medical College of Georgia. "Understanding Cell Death May Bring New Life To Kidney Treatment." ScienceDaily. ScienceDaily, 15 April 2006. <www.sciencedaily.com/releases/2006/04/060415112107.htm>.
Medical College of Georgia. (2006, April 15). Understanding Cell Death May Bring New Life To Kidney Treatment. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2006/04/060415112107.htm
Medical College of Georgia. "Understanding Cell Death May Bring New Life To Kidney Treatment." ScienceDaily. www.sciencedaily.com/releases/2006/04/060415112107.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Global Ebola Aid Increasing But Critics Say It's Late

Global Ebola Aid Increasing But Critics Say It's Late

Newsy (Sep. 21, 2014) More than 100 tons of medical supplies were sent to West Africa on Saturday, but aid workers say the global response is still sluggish. Video provided by Newsy
Powered by NewsLook.com
Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins