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: Fighting bacteria—with viruses

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

add to favorites email to friend print save as pdf

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

Fighting bacteria—with viruses

Jul 24, 2014

Research published today in PLOS Pathogens reveals how viruses called bacteriophages destroy the bacterium Clostridium difficile (C. diff), which is becoming a serious problem in hospitals and healthcare institutes, due to its re ...

Atomic structure of key muscle component revealed

Jul 24, 2014

Actin is the most abundant protein in the body, and when you look more closely at its fundamental role in life, it's easy to see why. It is the basis of most movement in the body, and all cells and components ...

Brand new technology detects probiotic organisms in food

Jul 23, 2014

In the food industr, ity is very important to ensure the quality and safety of products consumed by the population to improve their properties and reduce foodborne illness. Therefore, a team of Mexican researchers ...

Protein evolution follows a modular principle

Jul 23, 2014

Proteins impart shape and stability to cells, drive metabolic processes and transmit signals. To perform these manifold tasks, they fold into complex three-dimensional shapes. Scientists at the Max Planck ...

Report on viruses looks beyond disease

Jul 22, 2014

In contrast to their negative reputation as disease causing agents, some viruses can perform crucial biological and evolutionary functions that help to shape the world we live in today, according to a new report by the American ...

User comments : 0