2009年,人类肝脏蛋白质组计划(HLPP)的研究人员在 JPR(DOI 10.1021/pr900532r)上发表人类肝脏蛋白质组的一期 |
研究结果,文章共鉴定了6788个高可信度的中国成人肝脏蛋白质,是迄今最大规模的人体器官蛋白质组数据集。目前,表达 |
谱数据及相应的分析结果已分别整合成两个数据集,通过网站发布:dbLEP(http://dblep.hupo.org.cn); |
Liverbase(http://liverbase.hupo.org.cn)。 |
来源:http://pubs.acs.org/doi/full/10.1021/pr9007464?cookieSet=1 |
Mammoth data set from human liver reported |
A consortium of researchers report in JPR (2009, DOI 10.1021/pr900532r) their initial analysis of the |
human liver proteome, having assembled the largest proteomics data set yet for a human organ. The |
expression data has been compiled into two databases: Human Liver Expression Profile (dbLEP; |
http://dblep.hupo.org.cn) and Liverbase (http://liverbase.hupo.org.cn). |
The liver plays multiple essential roles in physiology—it produces digestive enzymes, hormones, and |
most of the proteins in the blood, and it stores glycogen and breaks down drugs. |
Project chairman Fuchu He at the State Key Laboratory of Proteomics, Beijing Proteome Research |
Center, and the Beijing Institute of Radiation Medicine says that investigating liver proteins is |
especially important for Chinese medicine because of the prevalence of hepatitis and liver cancer in |
China. |
The Human Liver Proteome Project (HLPP) was launched in 2002 as the first project of the Human |
Proteome Initiative for human organs and tissues, and also one of the first international |
collaborations in the life sciences to be led by China. As a close alliance with HLPP, the overall |
program of the Chinese Human Liver Proteome Project was initiated in 2004 by the Ministry of Science |
and Technology. Eleven laboratories were involved in a subproject devoted to expression profiling. |
Tissue samples were obtained from 10 adult volunteers undergoing surgery for hepatic hemangioma (a |
benign tumor of blood vessels) in 2005. |
The researchers used four standard techniques to separate either digested peptides or whole proteins |
before identifying them via MS. Each approach was duplicated at two of the participating centers, |
and each method was duplicated at least three times. |
A total of 6788 proteins were identified, though that number excludes >6000 proteins that had only |
one peptide match and were eliminated from the final count. The researchers identified proteins |
corresponding to ~60% of all of the protein-encoding genes expressed in liver, which were identified |
by RNA analysis from the same samples. |
Proteins involved in liver-specific functions, such as bile transport, bile acid synthesis, and |
bilirubin metabolism, were well-represented in the liver proteome. Also heavily represented were |
proteins involved in metabolism, nutrient transport, and blood coagulation, as well as complement |
proteins. In the signal transduction realm, the liver was well-covered in areas such as MAP kinase |
pathways, calcium, adhesion, insulin, and adipocytokine signaling, but low in other parts. |
Some 3721 of the identified proteins had not been seen in human liver before, though they had been |
detected in other human organs. Almost 1000 were “hypothetical”—their existence previously |
inferred from DNA sequence information only. |
Most (82.5%) of the newly identified liver proteins are present in low abundance. An intriguing |
finding is that many of the newly identified proteins appear to be related to pathological processes |
in the nervous system, according to the authors’ analysis using the Kyoto Encyclopedia of Genes and |
Genomes database. |
Humans have 57 members of the cytochrome p450 enzyme family, which are critical for metabolizing and |
activating drugs. Of these, the liver proteome team identified 31, and 4 were seen for the first |
time in human liver. |
About one-quarter of the members of the cytochrome p450 family are devoted to steroid hormones, and |
another chunk is involved in handling prostaglandins and fat-soluble vitamins, says Frederick |
Guengerich, director of molecular toxicology at the Vanderbilt University School of Medicine. “So |
you wouldn’t expect all of those to be expressed in the liver, but rather in the adrenals, the |
ovaries, and other endocrine organs,” he says. “Seeing 31 family members in the liver seems like |
reasonably good coverage.” |
Similarly, three ion-channel proteins, which tend to be low-abundance and difficult to extract, were |
seen for the first time in human liver by the liver proteome team. |
“It’s a very comprehensive baseline,” says Anand Mehta, who studies liver cancer biomarkers at the |
Drexel University College of Medicine. Groups such as his have performed comparisons of normal liver |
and diseased liver previously, “but this kind of breadth of coverage has not been achieved before.” |
Mehta expressed some concern that the volunteers’ hemangiomas may have had some distorting effect |
on the “normal liver” proteins, but he says the effects should become more apparent as more |
comparisons between normal and diseased states are conducted. |
Project coordinator Junjie Zheng, an assistant to He, says the team plans to refine its protein |
separation and analysis techniques. “From a technological perspective, the quality of this proteome |
will be improved by the development of higher-performance methods of protein separation, more |
sensitive and accurate methods of protein identification, and advances in data mining,” he says. |
“Ultimately, the proteomes of the individual cell types that make up the liver, as well as their |
organelles, will be profiled.” |
In addition, follow-up work with different developmental stages and comparisons of normal liver |
versus liver affected by diseases such as hepatitis B, fibrosis, cirrhosis, or hepatocellular |
carcinoma are also in progress, he says. |
首次报道人肝脏蛋白质组大规模数据
作者:北京蛋白质组研究中心 2009-11-20T00:00 (访问量:8217)
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