Abstract
Mallory bodies (MBs) are aggregates of proteins, principally cytokeratin proteins found in liver cells. They are also found in a few other cell types such as type II pneumocytes and trophoblasts. Studies on the liver thus far indicate that MBs are derived from hyperphosphorylated, heavily ubiquitinated proteins which have undergone conformational change. The aggregated protein may accumulate because of the failure of the proteasome to remove the altered proteins from the cytoplasm of liver cells. To investigate this possibility, the proteasomes were assessed immunohistochemically in individual liver cells of mice fed a drug which induced MB formation. To accelerate and enhance MB formation, cytochrome P450 2EI knockout mice were used. Proteasomes in individual cells were visualized by immunofluorescence using an antibody to a subunit of the proteasome (P25). The results showed that the groups of liver cells that had formed MBs were often partially depleted of proteasomes. These findings support the possibility that MBs formed as a result of the loss of the proteasome to remove misfolded cytokeratin proteins. Thus MBs may share their pathogenesis with other types of cellular inclusions seen where proteins aggregate in the cytoplasm due to mutation, misfolding, or loss of proteasomes.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7-18 |
| Number of pages | 12 |
| Journal | Experimental and Molecular Pathology |
| Volume | 70 |
| Issue number | 1 |
| DOIs | |
| State | Published - 2001 |
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Keywords
- Aggresome
- Conformational change
- CYP2E1
- Digestion
- Phosphorylation
- Proteasome
- Ubiquitination
ASJC Scopus subject areas
- Clinical Biochemistry
- Molecular Biology
- Pathology and Forensic Medicine
Cite this
Mallory bodies formed in proteasome-depleted hepatocytes : An immunohistochemical study. / Bardag-Gorce, Fawzia; French, Barbara Alan; Lue, Yan He; Nguyen, Victoria; Wan, Yu-Jui Yvonne; French, Samuel W.
In: Experimental and Molecular Pathology, Vol. 70, No. 1, 2001, p. 7-18.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mallory bodies formed in proteasome-depleted hepatocytes
T2 - An immunohistochemical study
AU - Bardag-Gorce, Fawzia
AU - French, Barbara Alan
AU - Lue, Yan He
AU - Nguyen, Victoria
AU - Wan, Yu-Jui Yvonne
AU - French, Samuel W.
PY - 2001
Y1 - 2001
N2 - Mallory bodies (MBs) are aggregates of proteins, principally cytokeratin proteins found in liver cells. They are also found in a few other cell types such as type II pneumocytes and trophoblasts. Studies on the liver thus far indicate that MBs are derived from hyperphosphorylated, heavily ubiquitinated proteins which have undergone conformational change. The aggregated protein may accumulate because of the failure of the proteasome to remove the altered proteins from the cytoplasm of liver cells. To investigate this possibility, the proteasomes were assessed immunohistochemically in individual liver cells of mice fed a drug which induced MB formation. To accelerate and enhance MB formation, cytochrome P450 2EI knockout mice were used. Proteasomes in individual cells were visualized by immunofluorescence using an antibody to a subunit of the proteasome (P25). The results showed that the groups of liver cells that had formed MBs were often partially depleted of proteasomes. These findings support the possibility that MBs formed as a result of the loss of the proteasome to remove misfolded cytokeratin proteins. Thus MBs may share their pathogenesis with other types of cellular inclusions seen where proteins aggregate in the cytoplasm due to mutation, misfolding, or loss of proteasomes.
AB - Mallory bodies (MBs) are aggregates of proteins, principally cytokeratin proteins found in liver cells. They are also found in a few other cell types such as type II pneumocytes and trophoblasts. Studies on the liver thus far indicate that MBs are derived from hyperphosphorylated, heavily ubiquitinated proteins which have undergone conformational change. The aggregated protein may accumulate because of the failure of the proteasome to remove the altered proteins from the cytoplasm of liver cells. To investigate this possibility, the proteasomes were assessed immunohistochemically in individual liver cells of mice fed a drug which induced MB formation. To accelerate and enhance MB formation, cytochrome P450 2EI knockout mice were used. Proteasomes in individual cells were visualized by immunofluorescence using an antibody to a subunit of the proteasome (P25). The results showed that the groups of liver cells that had formed MBs were often partially depleted of proteasomes. These findings support the possibility that MBs formed as a result of the loss of the proteasome to remove misfolded cytokeratin proteins. Thus MBs may share their pathogenesis with other types of cellular inclusions seen where proteins aggregate in the cytoplasm due to mutation, misfolding, or loss of proteasomes.
KW - Aggresome
KW - Conformational change
KW - CYP2E1
KW - Digestion
KW - Phosphorylation
KW - Proteasome
KW - Ubiquitination
UR - http://www.scopus.com/inward/record.url?scp=0035570009&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0035570009&partnerID=8YFLogxK
U2 - 10.1006/exmp.2000.2343
DO - 10.1006/exmp.2000.2343
M3 - Article
C2 - 11170786
AN - SCOPUS:0035570009
VL - 70
SP - 7
EP - 18
JO - Experimental and Molecular Pathology
JF - Experimental and Molecular Pathology
SN - 0014-4800
IS - 1
ER -