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Activated protein C induces endoplasmic reticulum stress and attenuates lipopolysaccharide-induced apoptosis mediated by glycogen synthase kinase-3β.

Luo L, Lv T, Wang Q, Zhang T, Gu X, Xu F, Song Y - Mediators Inflamm. (2012)

Bottom Line: Calcium inhibition did not alter the antiapoptotic effect of activated protein C.The antiapoptotic efficiency of activated protein C was reduced in human umbilical vein endothelial cells following treatment with glycogen synthase kinase-3β-siRNA.In summary, activated protein C induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis mediated by glycogen synthase kinase-3β.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.

ABSTRACT
This study investigated the relationship between antiapoptotic activities induced by activated protein C and endoplasmic reticulum stress. In this study, it was observed that activated protein C elicited a rise in glucose-regulated protein 78 and glycogen synthase kinase-3β and inhibited apoptosis in human umbilical vein endothelial cells induced by lipopolysaccharide. Calcium inhibition did not alter the antiapoptotic effect of activated protein C. The antiapoptotic efficiency of activated protein C was reduced in human umbilical vein endothelial cells following treatment with glycogen synthase kinase-3β-siRNA. In summary, activated protein C induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis mediated by glycogen synthase kinase-3β.

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Related in: MedlinePlus

APC-induced GRP78 expression in the presence and absence of LPS stimulation. Following HUVEC treatment with 150 nM APC for 0, 6, 12, and 24 h, upregulated GRP78 expression was initially detected at 6 h by Western blot analysis (GRP78 (a), P < 0.05), and then generally decreased. After continuous exposure to 10 ng/mL LPS for 24 h, HUVECs were treated with 150 nM APC for 0, 6, 12, and 24 h. Upregulated GRP78 expression was also detected at 6 h by Western blot analysis (GRP78 (b), P < 0.05), and then generally decreased. A significant difference in APC-induced GRP78 expression in the presence (b) and absence (a) of LPS stimulation was detected at 6 h, which indicated that 150 nM APC plays a more significant role in this effect following LPS stimulation (P < 0.05).
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fig2: APC-induced GRP78 expression in the presence and absence of LPS stimulation. Following HUVEC treatment with 150 nM APC for 0, 6, 12, and 24 h, upregulated GRP78 expression was initially detected at 6 h by Western blot analysis (GRP78 (a), P < 0.05), and then generally decreased. After continuous exposure to 10 ng/mL LPS for 24 h, HUVECs were treated with 150 nM APC for 0, 6, 12, and 24 h. Upregulated GRP78 expression was also detected at 6 h by Western blot analysis (GRP78 (b), P < 0.05), and then generally decreased. A significant difference in APC-induced GRP78 expression in the presence (b) and absence (a) of LPS stimulation was detected at 6 h, which indicated that 150 nM APC plays a more significant role in this effect following LPS stimulation (P < 0.05).

Mentions: Evidence has been obtained in previous studies that 150 nM APC induces a transient rise in calcium release from ER in HUVECs, implying an ER disturbance evoked by APC [13]. To investigate ER stress induced by APC, the effect of an ER-stress-related protein, GRP78 on HUVECs was examined following exposure for 0, 6, 12, 24 h. APC treatment upregulated GRP78 protein expression at 6 h (Figure 2). Upregulated GRP78 is responsible for the UPR in the ER. Therefore, these data indicate that APC acts as an ER stressor and elicits the UPR.


Activated protein C induces endoplasmic reticulum stress and attenuates lipopolysaccharide-induced apoptosis mediated by glycogen synthase kinase-3β.

Luo L, Lv T, Wang Q, Zhang T, Gu X, Xu F, Song Y - Mediators Inflamm. (2012)

APC-induced GRP78 expression in the presence and absence of LPS stimulation. Following HUVEC treatment with 150 nM APC for 0, 6, 12, and 24 h, upregulated GRP78 expression was initially detected at 6 h by Western blot analysis (GRP78 (a), P < 0.05), and then generally decreased. After continuous exposure to 10 ng/mL LPS for 24 h, HUVECs were treated with 150 nM APC for 0, 6, 12, and 24 h. Upregulated GRP78 expression was also detected at 6 h by Western blot analysis (GRP78 (b), P < 0.05), and then generally decreased. A significant difference in APC-induced GRP78 expression in the presence (b) and absence (a) of LPS stimulation was detected at 6 h, which indicated that 150 nM APC plays a more significant role in this effect following LPS stimulation (P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368528&req=5

fig2: APC-induced GRP78 expression in the presence and absence of LPS stimulation. Following HUVEC treatment with 150 nM APC for 0, 6, 12, and 24 h, upregulated GRP78 expression was initially detected at 6 h by Western blot analysis (GRP78 (a), P < 0.05), and then generally decreased. After continuous exposure to 10 ng/mL LPS for 24 h, HUVECs were treated with 150 nM APC for 0, 6, 12, and 24 h. Upregulated GRP78 expression was also detected at 6 h by Western blot analysis (GRP78 (b), P < 0.05), and then generally decreased. A significant difference in APC-induced GRP78 expression in the presence (b) and absence (a) of LPS stimulation was detected at 6 h, which indicated that 150 nM APC plays a more significant role in this effect following LPS stimulation (P < 0.05).
Mentions: Evidence has been obtained in previous studies that 150 nM APC induces a transient rise in calcium release from ER in HUVECs, implying an ER disturbance evoked by APC [13]. To investigate ER stress induced by APC, the effect of an ER-stress-related protein, GRP78 on HUVECs was examined following exposure for 0, 6, 12, 24 h. APC treatment upregulated GRP78 protein expression at 6 h (Figure 2). Upregulated GRP78 is responsible for the UPR in the ER. Therefore, these data indicate that APC acts as an ER stressor and elicits the UPR.

Bottom Line: Calcium inhibition did not alter the antiapoptotic effect of activated protein C.The antiapoptotic efficiency of activated protein C was reduced in human umbilical vein endothelial cells following treatment with glycogen synthase kinase-3β-siRNA.In summary, activated protein C induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis mediated by glycogen synthase kinase-3β.

View Article: PubMed Central - PubMed

Affiliation: Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.

ABSTRACT
This study investigated the relationship between antiapoptotic activities induced by activated protein C and endoplasmic reticulum stress. In this study, it was observed that activated protein C elicited a rise in glucose-regulated protein 78 and glycogen synthase kinase-3β and inhibited apoptosis in human umbilical vein endothelial cells induced by lipopolysaccharide. Calcium inhibition did not alter the antiapoptotic effect of activated protein C. The antiapoptotic efficiency of activated protein C was reduced in human umbilical vein endothelial cells following treatment with glycogen synthase kinase-3β-siRNA. In summary, activated protein C induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis mediated by glycogen synthase kinase-3β.

Show MeSH
Related in: MedlinePlus