Good housekeeping maintains a healthy liver

Oct 17, 2011
A new study in the Journal of Cell Biology suggests that differential expression of GAPDH and NDPK, two key metabolic enzymes, may explain why some people are more susceptible to liver damage.Compared to control cells (left), liver cells lacking GAPDH (right) show increased levels of reactive oxygen species (green) after treatment with the liver-damaging drug DDC. Credit: Image courtesy of Snider, N.T., et al. 2011. J. Cell Biol. doi:10.1083/jcb.201102142

Differences in the levels of two key metabolic enzymes may explain why some people are more susceptible to liver damage, according to a study in the October 17 issue of the Journal of Cell Biology.

Some forms of liver disease, particularly steatohepatitis, are marked by the formation of misfolded protein aggregates called Mallory-Denk bodies (MDBs). Not all patients display these aggregates, however, and some research suggests that MDBs are more common in patients of Hispanic origin. Different strains of mice also show different susceptibilities to MDB formation when their livers are damaged by the drug DDC, which induces oxidative stress. A team led by researchers from the University of Michigan analyzed the proteomes of livers from two different to investigate the cause of their different sensitivities to DDC.

Many metabolic and oxidative stress–related enzymes were expressed at differing levels in the livers of C57BL (MDB-susceptible) and C3H (MDB-resistant) mice, resulting in higher levels of reactive oxygen species in C57BL liver cells after DDC treatment. Prominent among these enzymes were two general "housekeeping" proteins: the metabolic enzyme GAPDH and the energy-generating protein NDPK, both of which showed reduced expression in C57BL livers and were decreased further by DDC treatment.

Depleting GAPDH or NDPK by RNAi elevated reactive oxygen species levels similarly to DDC treatment, whereas overexpressing GAPDH prevented DDC from inducing reactive oxygen species production in C57BL liver cells. The authors think that low GAPDH and NDPK expression causes C57BL livers to be metabolically and oxidatively stressed even under normal conditions and therefore more sensitive to additional stresses like DDC treatment. The researchers also found that GAPDH is localized in in cirrhotic patient livers, suggesting that similar mechanisms may contribute to liver disease severity in humans.

Explore further: Compound from soil microbe inhibits biofilm formation

More information: Snider, N.T., et al. 2011. J. Cell Biol. doi:10.1083/jcb.201102142

Related Stories

Keeping hepatitis C virus at bay after a liver transplant

Oct 01, 2009

One of the most common reasons for needing a liver transplant is liver failure or liver cancer caused by liver cell infection with hepatitis C virus (HCV). However, in nearly all patients the new liver becomes infected with ...

Recommended for you

Compound from soil microbe inhibits biofilm formation

9 hours ago

Researchers have shown that a known antibiotic and antifungal compound produced by a soil microbe can inhibit another species of microbe from forming biofilms—microbial mats that frequently are medically harmful—without ...

Researcher among best in protein modeling contests

12 hours ago

A Purdue University researcher ranks among the best in the world in bioinformatics competitions to predict protein structure, docking and function, making him a triple threat in the world of protein modeling.

Survey of salmonella species in Staten Island Zoo's snakes

13 hours ago

For humans, Salmonella is always bad news. The bacterial pathogen causes paratyphoid fever, gastroenteritis and typhoid. But for snakes, the bacteria aren't always bad news. Certain species of Salmonella are a natural part ...

A long-standing mystery in membrane traffic solved

Mar 27, 2015

In 2013, James E. Rothman, Randy W. Schekman, and Thomas C. Südhof won the Nobel Prize in Physiology or Medicine for their discoveries of molecular machineries for vesicle trafficking, a major transport ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.