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Proteomic analysis of regenerating mouse liver following 50% partial hepatectomy.

Cao H, Yu J, Xu W, Jia X, Yang J, Pan Q, Zhang Q, Sheng G, Li J, Pan X, Wang Y, Li L - Proteome Sci (2009)

Bottom Line: Remarkably, over 25 differentially expressed proteins were located at mitochondria.Several of the mitochondria-resident proteins which play important roles in citric acid cycle, oxidative phosphorylation and ATP production were found to be down-regulated, consistent with the recently-proposed model in which the reduction of ATP content in the remnant liver gives rise to early stress signals that contribute to the onset of liver regeneration.Our study provides novel evidence for mitochondria as a pivotal organelle that is connected to liver regeneration, and lays the foundation for further studies on key factors and pathways involved in liver regeneration following 50% PH, a condition frequently used for partial liver transplantation and conservative liver resection.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, 1st Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, PR China.

ABSTRACT

Background: Although 70% (or 2/3) partial hepatectomy (PH) is the most studied model for liver regeneration, the hepatic protein expression profile associated with lower volume liver resection (such as 50% PH) has not yet been reported. Therefore, the aim of this study was to determine the global protein expression profile of the regenerating mouse liver following 50% PH by differential proteomics, and thereby gaining some insights into the hepatic regeneration mechanism(s) under this milder but clinically more relevant condition.

Results: Proteins from sham-operated mouse livers and livers regenerating for 24 h after 50% PH were separated by SDS-PAGE and analyzed by nanoUPLC-Q-Tof mass spectrometry. Compared to sham-operated group, there were totally 87 differentially expressed proteins (with 50 up-regulated and 37 down-regulated ones) identified in the regenerating mouse livers, most of which have not been previously related to liver regeneration. Remarkably, over 25 differentially expressed proteins were located at mitochondria. Several of the mitochondria-resident proteins which play important roles in citric acid cycle, oxidative phosphorylation and ATP production were found to be down-regulated, consistent with the recently-proposed model in which the reduction of ATP content in the remnant liver gives rise to early stress signals that contribute to the onset of liver regeneration. Pathway analysis revealed a central role of c-Myc in the regulation of liver regeneration.

Conclusions: Our study provides novel evidence for mitochondria as a pivotal organelle that is connected to liver regeneration, and lays the foundation for further studies on key factors and pathways involved in liver regeneration following 50% PH, a condition frequently used for partial liver transplantation and conservative liver resection.

No MeSH data available.


Related in: MedlinePlus

Pathway analysis result showing 18 differentially expressed proteins following 50% PH can be sorted into the c-myc pathway. There are 18 root nodes in the sub-network shown, of which ACAA2, ALDH2, ACOX1, GSTP1, ACADM, ASS1(ASSY) are up-regulated and VDAC1, MGST, RPL11, ALDX, RPS5 are "newly-induced" in response to 50% PH; ACTG1(Actin cytoplasmic 2), HSPA8(HSC70), CAT(catalase) are down-regulated and FAH(FAAA), NDUFS3, RPS10, eEF1A2 are below detection limit. These root nodes are connected to c-Myc directly or indirectly, and their expression levels or activities can be regulated by c-Myc, and some of them (such as RPL11) can regulate c-Myc activity in a feedback manner. Legend describing symbols in the network can be found in Additional file 1.
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Figure 4: Pathway analysis result showing 18 differentially expressed proteins following 50% PH can be sorted into the c-myc pathway. There are 18 root nodes in the sub-network shown, of which ACAA2, ALDH2, ACOX1, GSTP1, ACADM, ASS1(ASSY) are up-regulated and VDAC1, MGST, RPL11, ALDX, RPS5 are "newly-induced" in response to 50% PH; ACTG1(Actin cytoplasmic 2), HSPA8(HSC70), CAT(catalase) are down-regulated and FAH(FAAA), NDUFS3, RPS10, eEF1A2 are below detection limit. These root nodes are connected to c-Myc directly or indirectly, and their expression levels or activities can be regulated by c-Myc, and some of them (such as RPL11) can regulate c-Myc activity in a feedback manner. Legend describing symbols in the network can be found in Additional file 1.

Mentions: When all the 87 differentially-expressed proteins were pooled together for pathway analysis, 18 of them can be clustered into the same pathway and connected to each other in one way or another (Fig. 4 and Additional file 1). c-Myc situates at the center of this network. Among them, ACAA2, ALDH2, ACOX1, GSTP1, ACADM, ASS1(ASSY) were up-regulated and VDAC1, MGST, RPL11, ALDX, RPS5 were "newly-induced" in response to 50% PH; ACTG1(Actin cytoplasmic 2), HSPA8(HSC70), CAT(catalase) were down-regulated and FAH(FAAA), NDUFS3, RPS10, eEF1A2 were below detection limit.


Proteomic analysis of regenerating mouse liver following 50% partial hepatectomy.

Cao H, Yu J, Xu W, Jia X, Yang J, Pan Q, Zhang Q, Sheng G, Li J, Pan X, Wang Y, Li L - Proteome Sci (2009)

Pathway analysis result showing 18 differentially expressed proteins following 50% PH can be sorted into the c-myc pathway. There are 18 root nodes in the sub-network shown, of which ACAA2, ALDH2, ACOX1, GSTP1, ACADM, ASS1(ASSY) are up-regulated and VDAC1, MGST, RPL11, ALDX, RPS5 are "newly-induced" in response to 50% PH; ACTG1(Actin cytoplasmic 2), HSPA8(HSC70), CAT(catalase) are down-regulated and FAH(FAAA), NDUFS3, RPS10, eEF1A2 are below detection limit. These root nodes are connected to c-Myc directly or indirectly, and their expression levels or activities can be regulated by c-Myc, and some of them (such as RPL11) can regulate c-Myc activity in a feedback manner. Legend describing symbols in the network can be found in Additional file 1.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2813229&req=5

Figure 4: Pathway analysis result showing 18 differentially expressed proteins following 50% PH can be sorted into the c-myc pathway. There are 18 root nodes in the sub-network shown, of which ACAA2, ALDH2, ACOX1, GSTP1, ACADM, ASS1(ASSY) are up-regulated and VDAC1, MGST, RPL11, ALDX, RPS5 are "newly-induced" in response to 50% PH; ACTG1(Actin cytoplasmic 2), HSPA8(HSC70), CAT(catalase) are down-regulated and FAH(FAAA), NDUFS3, RPS10, eEF1A2 are below detection limit. These root nodes are connected to c-Myc directly or indirectly, and their expression levels or activities can be regulated by c-Myc, and some of them (such as RPL11) can regulate c-Myc activity in a feedback manner. Legend describing symbols in the network can be found in Additional file 1.
Mentions: When all the 87 differentially-expressed proteins were pooled together for pathway analysis, 18 of them can be clustered into the same pathway and connected to each other in one way or another (Fig. 4 and Additional file 1). c-Myc situates at the center of this network. Among them, ACAA2, ALDH2, ACOX1, GSTP1, ACADM, ASS1(ASSY) were up-regulated and VDAC1, MGST, RPL11, ALDX, RPS5 were "newly-induced" in response to 50% PH; ACTG1(Actin cytoplasmic 2), HSPA8(HSC70), CAT(catalase) were down-regulated and FAH(FAAA), NDUFS3, RPS10, eEF1A2 were below detection limit.

Bottom Line: Remarkably, over 25 differentially expressed proteins were located at mitochondria.Several of the mitochondria-resident proteins which play important roles in citric acid cycle, oxidative phosphorylation and ATP production were found to be down-regulated, consistent with the recently-proposed model in which the reduction of ATP content in the remnant liver gives rise to early stress signals that contribute to the onset of liver regeneration.Our study provides novel evidence for mitochondria as a pivotal organelle that is connected to liver regeneration, and lays the foundation for further studies on key factors and pathways involved in liver regeneration following 50% PH, a condition frequently used for partial liver transplantation and conservative liver resection.

View Article: PubMed Central - HTML - PubMed

Affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, 1st Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, PR China.

ABSTRACT

Background: Although 70% (or 2/3) partial hepatectomy (PH) is the most studied model for liver regeneration, the hepatic protein expression profile associated with lower volume liver resection (such as 50% PH) has not yet been reported. Therefore, the aim of this study was to determine the global protein expression profile of the regenerating mouse liver following 50% PH by differential proteomics, and thereby gaining some insights into the hepatic regeneration mechanism(s) under this milder but clinically more relevant condition.

Results: Proteins from sham-operated mouse livers and livers regenerating for 24 h after 50% PH were separated by SDS-PAGE and analyzed by nanoUPLC-Q-Tof mass spectrometry. Compared to sham-operated group, there were totally 87 differentially expressed proteins (with 50 up-regulated and 37 down-regulated ones) identified in the regenerating mouse livers, most of which have not been previously related to liver regeneration. Remarkably, over 25 differentially expressed proteins were located at mitochondria. Several of the mitochondria-resident proteins which play important roles in citric acid cycle, oxidative phosphorylation and ATP production were found to be down-regulated, consistent with the recently-proposed model in which the reduction of ATP content in the remnant liver gives rise to early stress signals that contribute to the onset of liver regeneration. Pathway analysis revealed a central role of c-Myc in the regulation of liver regeneration.

Conclusions: Our study provides novel evidence for mitochondria as a pivotal organelle that is connected to liver regeneration, and lays the foundation for further studies on key factors and pathways involved in liver regeneration following 50% PH, a condition frequently used for partial liver transplantation and conservative liver resection.

No MeSH data available.


Related in: MedlinePlus