Proteomics of starvation
KAATJE LENAERTS
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expression patterns.” The levels of prolonged starvation conditions. Even in the 21st century, hunger is a some proteins could have returned to Intestinal cells made a last-ditch effort to protect themselves after 24 h. pressing problem. Millions of people normal, but Lenaerts says that an alterFor example, levels of glutathione per worldwide die from starvation and malnative explanation is that the variation oxidase 3, an extracellular protein that nutrition every year, primarily because in the 72-h group was larger than in the they don’t have enough money to buy other groups. staves off damage from oxidative stress, healthful food. But poverty is not the To pinpoint the progression of events increased slowly as starvation condionly reason people starve. For example, in starvation, the researchers identified tions persisted. The proteins reg I and those suffering from anorexia nervosa several of the differentially regulated reg II also were up-regulated by 72 h. have an intense fear of gaining weight proteins. During the first 12 h of depri“I found [these proteins] to be quite surprising because if you look at the and refuse to eat. Other people starve vation, energy-related proteins were themselves because they’ve heard in decline. The levels of energy-meliterature, they are often linked to the about the research sugpancreas, but we found gesting that a reduction them here to be functionCellular of caloric intake may al in the small intestine,” Villus protection prolong their life spans. says Lenaerts. Reg I and morphogenesis mechanisms But what drove Kaatje reg II “are important for Lenaerts at Maastricht the intestinal regeneraUniversity (The Nethtion after an insult,” she erlands) to the study of explains. The cytoskeletal Mouse starvation was observprotein ezrin, which is a small ing patients who were structural element in the 12 h 24 h 72 h intestine suffering from critical villus, also was up-reguillnesses. These patients lated. Lenaerts says that are very sick and are fed the increase in ezrin may intravenously. “In this help the small intestine situation, [clinicians] to quickly absorb any nuGlucose and Protein see atrophy of the intestrients that are ingested energy metabolism synthesis tinal cells” of patients, at this late stage of deprishe says. “We were vation. actually looking for a Lenaerts focused on Phases of starvation. Certain classes of proteins are up- or down-regulated in nutritional intervention proteomics analyses, the small intestine in response to prolonged food deprivation. to better assist intestinal whereas some of her function.” With this goal collaborators conducted in mind, Lenaerts and colleagues at tabolism enzymes, such as ubiquinolparallel transcriptomics experiments. Maastricht University and the Univercytochrome-c reductase complex core The results from these experiments will sity of Amsterdam used proteomics and protein I, decreased. Proteins involved be published in a separate paper. The transcriptomics approaches to assess in glycolysis also were down-regulated trends observed with the mRNA data the dynamic changes that occur in the in the absence of glucose intake. Some did not always match those observed body during starvation. In this issue proteins, however, were induced. For with the proteomics data, however. of JPR (pp 2113–2122), they report that example, several protein folding and Contradictory levels could be explained several proteins were differentially processing enzymes accumulated at by increased protein degradation or deregulated in mice that were starved for the 12-h time point. This finding “could creased translation efficiency. “Also, it various periods. be due to the fact that most of [these is possible that some proteins are modiIn the experiment, mice were deproteins] are stress proteins, and of fied so that they appear in another poprived of food for 0 (control), 12, 24, course, starvation is a stressful event sition in the gel,” says Lenaerts. In this or 72 h. The researchers analyzed the for the mice,” explains Lenaerts. case, a protein inadvertently may be proteins in the small intestine by 2DE. In the second phase of starvation counted as absent or down-regulated. Several spots were up- or down-regu(at 24 h), protein synthesis factors and The biggest challenge for the related in starved mice compared with amino acid metabolism proteins genersearchers is still to come, says Lenaerts. the control mice. After 12 h of starvaally were decreased in abundance. The “We see that the expression levels are tion, the abundances of 36 spots were researchers confirmed by immunochanged by starvation, but now, the altered. An additional 22 spots were histochemistry that levels of ornithine next [thing] is to see how these proteins different at the 24-h time point. Interaminotransferase, which converts gluinfluence the intestinal function,” she estingly, only 27 spots were changed at tamine to ornithine, declined over time explains. The researchers also plan to 72 h. According to Lenaerts, this result during starvation. “Apparently, glutaconduct another mouse study, in which “surprised us because you’d expect that mine levels should be high for the intesthey will try to counteract the effects this [time point] would be the most tine,” says Lenaerts. She adds that high of starvation by adding supplements to extreme condition, but it doesn’t seem amounts of glutamine could be used the drinking water. like that [when you look] at the protein by the intestine to produce glucose in —Katie Cottingham
Journal of Proteome Research • Vol. 5, No. 9, 2006 2075
