Limits...
The Hypothermic Influence on CHOP and Ero1-α in an Endoplasmic Reticulum Stress Model of Cerebral Ischemia.

Poone GK, Hasseldam H, Munkholm N, Rasmussen RS, Grønberg NV, Johansen FF - Brain Sci (2015)

Bottom Line: As a result of ischemia, a significant increase in expression of CHOP and Ero1-α was observed after three, six and twelve hours of reperfusion following global ischemia.On the contrary, the gene expression of Ero1-α increased as a result of hypothermia and peaked at twelve hours (p < 0.0001).As hypothermia further induced up-regulation of Ero1-α, and since CHOP and Ero1-α showed differential regulation as a consequence of both disease (hypoxia) and treatment (hypothermia), we conclude that they are regulated independently.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences and Biotech Research & Innovation Centre (BRIC), University of Copenhagen, 2200, Denmark. gagandipkb@hotmail.com.

ABSTRACT
Hypoxia induced endoplasmic reticulum stress causes accumulation of unfolded proteins in the endoplasmic reticulum and activates the unfolded protein response, resulting in apoptosis through CCAAT-enhancer-binding protein homologous protein (CHOP) activation. In an in vitro and in vivo model of ischemic stroke, we investigated whether hypothermia regulates the unfolded protein response of CHOP and Endoplasmic reticulum oxidoreductin-α (Ero1-α), because Ero1-α is suggested to be a downstream CHOP target. The gene expression of CHOP and Ero1-α was measured using Quantitative-PCR (Q-PCR) in rat hippocampi following global cerebral ischemia, and in hypoxic pheochromocytoma cells during normothermic (37 °C) and hypothermic (31 °C) conditions. As a result of ischemia, a significant increase in expression of CHOP and Ero1-α was observed after three, six and twelve hours of reperfusion following global ischemia. A stable increase in CHOP expression was observed throughout the time course (p < 0.01, p < 0.0001), whereas Ero1-α expression peaked at three to six hours (p < 0.0001). Induced hypothermia in hypoxia stressed PC12 cells resulted in a decreased expression of CHOP after three, six and twelve hours (p < 0.0001). On the contrary, the gene expression of Ero1-α increased as a result of hypothermia and peaked at twelve hours (p < 0.0001). Hypothermia attenuated the expression of CHOP, supporting that hypothermia suppress endoplasmic reticulum stress induced apoptosis in stroke. As hypothermia further induced up-regulation of Ero1-α, and since CHOP and Ero1-α showed differential regulation as a consequence of both disease (hypoxia) and treatment (hypothermia), we conclude that they are regulated independently.

No MeSH data available.


Related in: MedlinePlus

Hippocampal expression of CHOP and Ero1-α following global ischemia. Quantitative PCR revealed a significant increase in expression of CHOP and Ero1-α induced by global ischemia over a time course of 12 h. The greatest expression level of CHOP is detected at 6 h of reperfusion (n = 6) compared to untreated animals (n = 10), (p < 0.0001). At 3 h (n = 7) and 12 h (n = 6) after induction of ischemia similar expression levels of CHOP were observed, significantly greater than in the untreated group (p < 0.01). No difference between the different time points was detected. Ero1-α was significantly increased at 3 h (n = 5), 6 h (n = 7) and 12 h (n = 5) of reperfusion (p < 0.0001 and 0.01 respectively), with greatest expression levels at 3 to 6 h followed by a decrease. Data analyzed by one-way ANOVA followed by Tukey’s multiple comparisons test. ** p < 0.01 and **** p < 0.0001.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493463&req=5

brainsci-05-00178-f001: Hippocampal expression of CHOP and Ero1-α following global ischemia. Quantitative PCR revealed a significant increase in expression of CHOP and Ero1-α induced by global ischemia over a time course of 12 h. The greatest expression level of CHOP is detected at 6 h of reperfusion (n = 6) compared to untreated animals (n = 10), (p < 0.0001). At 3 h (n = 7) and 12 h (n = 6) after induction of ischemia similar expression levels of CHOP were observed, significantly greater than in the untreated group (p < 0.01). No difference between the different time points was detected. Ero1-α was significantly increased at 3 h (n = 5), 6 h (n = 7) and 12 h (n = 5) of reperfusion (p < 0.0001 and 0.01 respectively), with greatest expression levels at 3 to 6 h followed by a decrease. Data analyzed by one-way ANOVA followed by Tukey’s multiple comparisons test. ** p < 0.01 and **** p < 0.0001.

Mentions: Induction of global ischemia altered the expression level of CHOP and Ero1-α in hippocampi of Wistar rats (Figure 1). A stable CHOP increase was observed throughout the entire time course. At 3 and 12 h of reperfusion, CHOP was found to be significantly up-regulated compared to untreated, control animals (p < 0.01). At 6 h of reperfusion, CHOP levels were further increased (p < 0.0001), however not significantly different from the 3 and 12 h group. Similar to CHOP, Ero1-α was also increased at 3 to 6 h following ischemia (p < 0.0001), although it seemed to reach maximum at this time point and was reduced towards normal levels after 12 h of reperfusion. Nevertheless, 3, 6 and 12 h after ischemic injury all show significant up-regulation of Ero1-α compared to untreated controls (p < 0.0001 and 0.01 respectively).


The Hypothermic Influence on CHOP and Ero1-α in an Endoplasmic Reticulum Stress Model of Cerebral Ischemia.

Poone GK, Hasseldam H, Munkholm N, Rasmussen RS, Grønberg NV, Johansen FF - Brain Sci (2015)

Hippocampal expression of CHOP and Ero1-α following global ischemia. Quantitative PCR revealed a significant increase in expression of CHOP and Ero1-α induced by global ischemia over a time course of 12 h. The greatest expression level of CHOP is detected at 6 h of reperfusion (n = 6) compared to untreated animals (n = 10), (p < 0.0001). At 3 h (n = 7) and 12 h (n = 6) after induction of ischemia similar expression levels of CHOP were observed, significantly greater than in the untreated group (p < 0.01). No difference between the different time points was detected. Ero1-α was significantly increased at 3 h (n = 5), 6 h (n = 7) and 12 h (n = 5) of reperfusion (p < 0.0001 and 0.01 respectively), with greatest expression levels at 3 to 6 h followed by a decrease. Data analyzed by one-way ANOVA followed by Tukey’s multiple comparisons test. ** p < 0.01 and **** p < 0.0001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493463&req=5

brainsci-05-00178-f001: Hippocampal expression of CHOP and Ero1-α following global ischemia. Quantitative PCR revealed a significant increase in expression of CHOP and Ero1-α induced by global ischemia over a time course of 12 h. The greatest expression level of CHOP is detected at 6 h of reperfusion (n = 6) compared to untreated animals (n = 10), (p < 0.0001). At 3 h (n = 7) and 12 h (n = 6) after induction of ischemia similar expression levels of CHOP were observed, significantly greater than in the untreated group (p < 0.01). No difference between the different time points was detected. Ero1-α was significantly increased at 3 h (n = 5), 6 h (n = 7) and 12 h (n = 5) of reperfusion (p < 0.0001 and 0.01 respectively), with greatest expression levels at 3 to 6 h followed by a decrease. Data analyzed by one-way ANOVA followed by Tukey’s multiple comparisons test. ** p < 0.01 and **** p < 0.0001.
Mentions: Induction of global ischemia altered the expression level of CHOP and Ero1-α in hippocampi of Wistar rats (Figure 1). A stable CHOP increase was observed throughout the entire time course. At 3 and 12 h of reperfusion, CHOP was found to be significantly up-regulated compared to untreated, control animals (p < 0.01). At 6 h of reperfusion, CHOP levels were further increased (p < 0.0001), however not significantly different from the 3 and 12 h group. Similar to CHOP, Ero1-α was also increased at 3 to 6 h following ischemia (p < 0.0001), although it seemed to reach maximum at this time point and was reduced towards normal levels after 12 h of reperfusion. Nevertheless, 3, 6 and 12 h after ischemic injury all show significant up-regulation of Ero1-α compared to untreated controls (p < 0.0001 and 0.01 respectively).

Bottom Line: As a result of ischemia, a significant increase in expression of CHOP and Ero1-α was observed after three, six and twelve hours of reperfusion following global ischemia.On the contrary, the gene expression of Ero1-α increased as a result of hypothermia and peaked at twelve hours (p < 0.0001).As hypothermia further induced up-regulation of Ero1-α, and since CHOP and Ero1-α showed differential regulation as a consequence of both disease (hypoxia) and treatment (hypothermia), we conclude that they are regulated independently.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Sciences and Biotech Research & Innovation Centre (BRIC), University of Copenhagen, 2200, Denmark. gagandipkb@hotmail.com.

ABSTRACT
Hypoxia induced endoplasmic reticulum stress causes accumulation of unfolded proteins in the endoplasmic reticulum and activates the unfolded protein response, resulting in apoptosis through CCAAT-enhancer-binding protein homologous protein (CHOP) activation. In an in vitro and in vivo model of ischemic stroke, we investigated whether hypothermia regulates the unfolded protein response of CHOP and Endoplasmic reticulum oxidoreductin-α (Ero1-α), because Ero1-α is suggested to be a downstream CHOP target. The gene expression of CHOP and Ero1-α was measured using Quantitative-PCR (Q-PCR) in rat hippocampi following global cerebral ischemia, and in hypoxic pheochromocytoma cells during normothermic (37 °C) and hypothermic (31 °C) conditions. As a result of ischemia, a significant increase in expression of CHOP and Ero1-α was observed after three, six and twelve hours of reperfusion following global ischemia. A stable increase in CHOP expression was observed throughout the time course (p < 0.01, p < 0.0001), whereas Ero1-α expression peaked at three to six hours (p < 0.0001). Induced hypothermia in hypoxia stressed PC12 cells resulted in a decreased expression of CHOP after three, six and twelve hours (p < 0.0001). On the contrary, the gene expression of Ero1-α increased as a result of hypothermia and peaked at twelve hours (p < 0.0001). Hypothermia attenuated the expression of CHOP, supporting that hypothermia suppress endoplasmic reticulum stress induced apoptosis in stroke. As hypothermia further induced up-regulation of Ero1-α, and since CHOP and Ero1-α showed differential regulation as a consequence of both disease (hypoxia) and treatment (hypothermia), we conclude that they are regulated independently.

No MeSH data available.


Related in: MedlinePlus