Limits...
Curcumin ameliorates streptozotocin-induced liver damage through modulation of endoplasmic reticulum stress-mediated apoptosis in diabetic rats.

Afrin R, Arumugam S, Soetikno V, Thandavarayan RA, Pitchaimani V, Karuppagounder V, Sreedhar R, Harima M, Suzuki H, Miyashita S, Nomoto M, Suzuki K, Watanabe K - Free Radic. Res. (2015)

Bottom Line: Moreover, treatment with curcumin markedly decreased the sub-arm of the UPR signaling protein such as phospho-double-stranded RNA-dependent protein kinase-like ER kinase, CCAAT/enhancer-binding protein homologous protein, tumor necrosis factor receptor-associated factor 2, and inositol-requiring enzyme1α; and inhibited tumor necrosis factor α, interleukin 1β, phospho-p38 mitogen-activated protein kinase, and apoptosis signal-regulating kinase 1 in liver tissues of diabetic rats.Apoptotic and anti-apoptotic signaling proteins, such as cleaved caspase-3 and B-cell lymphoma 2, were significantly increased and decreased, respectively in diabetic rats; curcumin treatment prevented all of these alterations.In summary, our results indicate that curcumin has the potential to protect the diabetic liver by modulating hepatic ERS-mediated apoptosis, and provides a novel therapeutic strategy for the diabetic liver damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences , Niigata , Japan.

ABSTRACT
We investigated the effect of curcumin on liver injury in diabetic rats induced by streptozotocin (STZ) through modulation of endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). Experimental diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg), and curcumin was given at 100 mg/kg by gavage for 56 days. We observed that curcumin improved the morphological and histopathological changes, significantly decreased hepatic ERS marker protein: glucose-regulated protein 78, and improved liver function in diabetic rats. Moreover, treatment with curcumin markedly decreased the sub-arm of the UPR signaling protein such as phospho-double-stranded RNA-dependent protein kinase-like ER kinase, CCAAT/enhancer-binding protein homologous protein, tumor necrosis factor receptor-associated factor 2, and inositol-requiring enzyme1α; and inhibited tumor necrosis factor α, interleukin 1β, phospho-p38 mitogen-activated protein kinase, and apoptosis signal-regulating kinase 1 in liver tissues of diabetic rats. Apoptotic and anti-apoptotic signaling proteins, such as cleaved caspase-3 and B-cell lymphoma 2, were significantly increased and decreased, respectively in diabetic rats; curcumin treatment prevented all of these alterations. In summary, our results indicate that curcumin has the potential to protect the diabetic liver by modulating hepatic ERS-mediated apoptosis, and provides a novel therapeutic strategy for the diabetic liver damage.

Show MeSH

Related in: MedlinePlus

Expression of hepatic protein involved in ERS. Representative Western blots (lower panel) show specific bands for GRP78 (A) and Caspase-12 (B); representative histograms (upper panel) show the band densities with relative β-tubulin. The blots are representatives of five independent experiments. Each bar represents mean ± SE. Normal, age-matched normal rats; Control, untreated diabetic rats; Curcumin, diabetic rats treated with curcumin 100 mg/kg/day. ∗∗p < 0.01 versus Normal, #p < 0.05 versus Control based on one-way ANOVA followed by Tukey's test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4389763&req=5

Figure 2: Expression of hepatic protein involved in ERS. Representative Western blots (lower panel) show specific bands for GRP78 (A) and Caspase-12 (B); representative histograms (upper panel) show the band densities with relative β-tubulin. The blots are representatives of five independent experiments. Each bar represents mean ± SE. Normal, age-matched normal rats; Control, untreated diabetic rats; Curcumin, diabetic rats treated with curcumin 100 mg/kg/day. ∗∗p < 0.01 versus Normal, #p < 0.05 versus Control based on one-way ANOVA followed by Tukey's test.

Mentions: Activation of GRP78 protein expression was used to demonstrate the ERS induction, whose expression is reported to be increased in the diabetic rats. ERS leads to the activation of caspase-12 and other markers involved in the hepatic changes associated with diabetes mellitus. Our study with diabetic rats also revealed the involvement of ERS as evidenced by a significant increase in the hepatic GRP78 expression but cleaved caspase-12 expression was not so significant. Prevention of ERS is one of the strategies involved in the reduction of liver complications of diabetes. In the present study, curcumin-treated animals had shown significant attenuation of GRP78, and cleaved caspase-12 was slightly attenuated when compared with the control group (Figure 2A and B).


Curcumin ameliorates streptozotocin-induced liver damage through modulation of endoplasmic reticulum stress-mediated apoptosis in diabetic rats.

Afrin R, Arumugam S, Soetikno V, Thandavarayan RA, Pitchaimani V, Karuppagounder V, Sreedhar R, Harima M, Suzuki H, Miyashita S, Nomoto M, Suzuki K, Watanabe K - Free Radic. Res. (2015)

Expression of hepatic protein involved in ERS. Representative Western blots (lower panel) show specific bands for GRP78 (A) and Caspase-12 (B); representative histograms (upper panel) show the band densities with relative β-tubulin. The blots are representatives of five independent experiments. Each bar represents mean ± SE. Normal, age-matched normal rats; Control, untreated diabetic rats; Curcumin, diabetic rats treated with curcumin 100 mg/kg/day. ∗∗p < 0.01 versus Normal, #p < 0.05 versus Control based on one-way ANOVA followed by Tukey's test.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4389763&req=5

Figure 2: Expression of hepatic protein involved in ERS. Representative Western blots (lower panel) show specific bands for GRP78 (A) and Caspase-12 (B); representative histograms (upper panel) show the band densities with relative β-tubulin. The blots are representatives of five independent experiments. Each bar represents mean ± SE. Normal, age-matched normal rats; Control, untreated diabetic rats; Curcumin, diabetic rats treated with curcumin 100 mg/kg/day. ∗∗p < 0.01 versus Normal, #p < 0.05 versus Control based on one-way ANOVA followed by Tukey's test.
Mentions: Activation of GRP78 protein expression was used to demonstrate the ERS induction, whose expression is reported to be increased in the diabetic rats. ERS leads to the activation of caspase-12 and other markers involved in the hepatic changes associated with diabetes mellitus. Our study with diabetic rats also revealed the involvement of ERS as evidenced by a significant increase in the hepatic GRP78 expression but cleaved caspase-12 expression was not so significant. Prevention of ERS is one of the strategies involved in the reduction of liver complications of diabetes. In the present study, curcumin-treated animals had shown significant attenuation of GRP78, and cleaved caspase-12 was slightly attenuated when compared with the control group (Figure 2A and B).

Bottom Line: Moreover, treatment with curcumin markedly decreased the sub-arm of the UPR signaling protein such as phospho-double-stranded RNA-dependent protein kinase-like ER kinase, CCAAT/enhancer-binding protein homologous protein, tumor necrosis factor receptor-associated factor 2, and inositol-requiring enzyme1α; and inhibited tumor necrosis factor α, interleukin 1β, phospho-p38 mitogen-activated protein kinase, and apoptosis signal-regulating kinase 1 in liver tissues of diabetic rats.Apoptotic and anti-apoptotic signaling proteins, such as cleaved caspase-3 and B-cell lymphoma 2, were significantly increased and decreased, respectively in diabetic rats; curcumin treatment prevented all of these alterations.In summary, our results indicate that curcumin has the potential to protect the diabetic liver by modulating hepatic ERS-mediated apoptosis, and provides a novel therapeutic strategy for the diabetic liver damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences , Niigata , Japan.

ABSTRACT
We investigated the effect of curcumin on liver injury in diabetic rats induced by streptozotocin (STZ) through modulation of endoplasmic reticulum stress (ERS) and unfolded protein response (UPR). Experimental diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg), and curcumin was given at 100 mg/kg by gavage for 56 days. We observed that curcumin improved the morphological and histopathological changes, significantly decreased hepatic ERS marker protein: glucose-regulated protein 78, and improved liver function in diabetic rats. Moreover, treatment with curcumin markedly decreased the sub-arm of the UPR signaling protein such as phospho-double-stranded RNA-dependent protein kinase-like ER kinase, CCAAT/enhancer-binding protein homologous protein, tumor necrosis factor receptor-associated factor 2, and inositol-requiring enzyme1α; and inhibited tumor necrosis factor α, interleukin 1β, phospho-p38 mitogen-activated protein kinase, and apoptosis signal-regulating kinase 1 in liver tissues of diabetic rats. Apoptotic and anti-apoptotic signaling proteins, such as cleaved caspase-3 and B-cell lymphoma 2, were significantly increased and decreased, respectively in diabetic rats; curcumin treatment prevented all of these alterations. In summary, our results indicate that curcumin has the potential to protect the diabetic liver by modulating hepatic ERS-mediated apoptosis, and provides a novel therapeutic strategy for the diabetic liver damage.

Show MeSH
Related in: MedlinePlus