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Role of Exogenous Hsp72 on Liver Dysfunction during Sepsis.

Tsai TN, Ho JJ, Liu MS, Lee TY, Lu MC, Liu CJ, Huang LJ, Lue SI, Yang RC - Biomed Res Int (2015)

Bottom Line: Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining.B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting.The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

ABSTRACT
This study examined the role of exogenous heat shock protein 72 (Hsp72) in reversing sepsis-induced liver dysfunction. Sepsis was induced by cecal ligation and puncture. Liver function was determined on the basis of the enzymatic activities of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting. Results showed GOT and GPT levels increased during sepsis, and levels were restored following the administration of human recombinant Hsp72 (rhHsp72). Increased liver tissue apoptosis was observed during sepsis, and normal apoptosis resumed on rhHsp72 administration. The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment. We conclude that, during sepsis, exogenous Hsp72 restored liver dysfunction by inhibiting apoptosis via the mitochondria-initiated caspase pathway.

No MeSH data available.


Related in: MedlinePlus

Effects of rhHsp72 on the suppression of apoptotic mediator activation. Experiments were conducted as described in Section 2. Values are mean ± standard error of the mean. Each group contained 12 animals. ∗∗p < 0.01, and N.S. versus sham.
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fig4: Effects of rhHsp72 on the suppression of apoptotic mediator activation. Experiments were conducted as described in Section 2. Values are mean ± standard error of the mean. Each group contained 12 animals. ∗∗p < 0.01, and N.S. versus sham.

Mentions: Caspase-3, a prominent signaling molecule in the apoptosis pathway, is initiated by caspase-9 in the mitochondria-dependent pathway. Activated caspase-3 cleaves PARP, which in turn promotes DNA degradation. The results in Figures 4(a) and 4(b) reveal that the expression of activated caspase-3 and caspase-9 increased during sepsis (comparison between empty and black columns; +103.3%; ∗∗p < 0.001 and +40.9%; ∗∗p < 0.001). The sepsis-induced increase in the activated capase-3 and caspase-9 levels returned to the control levels after rhHsp72 administration (Figures 4(a) and 4(b), comparison between empty and shaded columns). The results in Figure 4(c) confirm that the protein expression of cleaved PARP was upregulated (comparison between empty and black columns; +1106%; ∗∗p < 0.001). The sepsis-induced upregulation of PARP expression returned to the control level after rhHsp72 administration (Figure 4(c), comparison between empty and shaded columns). These results suggest that the protective effects of rhHsp70 on liver cell apoptosis during sepsis progression are mediated through the suppression of apoptotic pathway mediators (i.e., activated caspase-3, activated caspase-9, and cleaved PARP).


Role of Exogenous Hsp72 on Liver Dysfunction during Sepsis.

Tsai TN, Ho JJ, Liu MS, Lee TY, Lu MC, Liu CJ, Huang LJ, Lue SI, Yang RC - Biomed Res Int (2015)

Effects of rhHsp72 on the suppression of apoptotic mediator activation. Experiments were conducted as described in Section 2. Values are mean ± standard error of the mean. Each group contained 12 animals. ∗∗p < 0.01, and N.S. versus sham.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4499656&req=5

fig4: Effects of rhHsp72 on the suppression of apoptotic mediator activation. Experiments were conducted as described in Section 2. Values are mean ± standard error of the mean. Each group contained 12 animals. ∗∗p < 0.01, and N.S. versus sham.
Mentions: Caspase-3, a prominent signaling molecule in the apoptosis pathway, is initiated by caspase-9 in the mitochondria-dependent pathway. Activated caspase-3 cleaves PARP, which in turn promotes DNA degradation. The results in Figures 4(a) and 4(b) reveal that the expression of activated caspase-3 and caspase-9 increased during sepsis (comparison between empty and black columns; +103.3%; ∗∗p < 0.001 and +40.9%; ∗∗p < 0.001). The sepsis-induced increase in the activated capase-3 and caspase-9 levels returned to the control levels after rhHsp72 administration (Figures 4(a) and 4(b), comparison between empty and shaded columns). The results in Figure 4(c) confirm that the protein expression of cleaved PARP was upregulated (comparison between empty and black columns; +1106%; ∗∗p < 0.001). The sepsis-induced upregulation of PARP expression returned to the control level after rhHsp72 administration (Figure 4(c), comparison between empty and shaded columns). These results suggest that the protective effects of rhHsp70 on liver cell apoptosis during sepsis progression are mediated through the suppression of apoptotic pathway mediators (i.e., activated caspase-3, activated caspase-9, and cleaved PARP).

Bottom Line: Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining.B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting.The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

ABSTRACT
This study examined the role of exogenous heat shock protein 72 (Hsp72) in reversing sepsis-induced liver dysfunction. Sepsis was induced by cecal ligation and puncture. Liver function was determined on the basis of the enzymatic activities of serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT). Apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling staining. B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), cleaved caspase-3 and caspase-9, and cleaved poly (ADP-ribose) polymerase (PARP) protein expressions were analyzed using Western blotting. Results showed GOT and GPT levels increased during sepsis, and levels were restored following the administration of human recombinant Hsp72 (rhHsp72). Increased liver tissue apoptosis was observed during sepsis, and normal apoptosis resumed on rhHsp72 administration. The Bcl-2/Bax ratio, cleaved caspase-3, caspase-9, and PARP protein expressions in the liver tissues were upregulated during sepsis and normalized after rhHsp72 treatment. We conclude that, during sepsis, exogenous Hsp72 restored liver dysfunction by inhibiting apoptosis via the mitochondria-initiated caspase pathway.

No MeSH data available.


Related in: MedlinePlus