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Hsp20 Protects against Oxygen-Glucose Deprivation/Reperfusion-Induced Golgi Fragmentation and Apoptosis through Fas/FasL Pathway.

Zhong B, Hu Z, Tan J, Lu T, Lei Q, Chen C, Zeng L - Oxid Med Cell Longev (2015)

Bottom Line: Finding effective neuroprotective agents has become a priority in the treatment of ischemic stroke.However, transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation and apoptosis.Hsp20 interacts with Bax, decreases FasL and Bax expression, and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China ; Department of Traditional Chinese Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

ABSTRACT
Cerebral ischemia-reperfusion injury plays an important role in the development of tissue injury after acute ischemic stroke. Finding effective neuroprotective agents has become a priority in the treatment of ischemic stroke. The Golgi apparatus (GA) is a pivotal organelle and its protection is an attractive target in the treatment of cerebral ischemia-reperfusion injury. Protective effects of Hsp20, a potential cytoprotective agent due to its chaperone-like activity and involvement in regulation of many vital processes, on GA were assessed in an ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces Golgi fragmentation, apoptosis, and p115 cleavage in N2a cells. However, transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation and apoptosis. Hsp20 interacts with Bax, decreases FasL and Bax expression, and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. Our data demonstrate that increased Hsp20 expression protects against OGDR-induced Golgi fragmentation and apoptosis, likely through interaction with Bax and subsequent amelioration of the OGDR-induced elevation in p115 cleavage via the Fas/FasL signaling pathway. This neuroprotective potential of Hsp20 against OGDR insult and the underlying mechanism will pave the way for its potential clinical application for cerebral ischemia-reperfusion related disorders.

No MeSH data available.


Related in: MedlinePlus

Hsp20 decreases FasL and Bax expression and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. The experiment was repeated independently for at least three times. (a) Effects of Hsp20 on apoptotic proteins expression and p115 cleavage in N2a Cells treated with OGD 4 h plus 12 h reperfusion. Transfection with Hsp20 decreased FasL and Bax expression and inhibited caspases 3 and p115 cleavage after 12 h reperfusion following 4 h OGD. (b) Quantitation (mean ± SEM) of (a) from three independent experiments. Values are expressed as mean ± SEM. ∗P < 0.05 compared to N2a Cells treated with OGD 4 h plus 12 h reperfusion. ∗∗P < 0.01 compared to N2a Cells treated with OGD 4 h plus 12 h reperfusion.
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fig5: Hsp20 decreases FasL and Bax expression and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. The experiment was repeated independently for at least three times. (a) Effects of Hsp20 on apoptotic proteins expression and p115 cleavage in N2a Cells treated with OGD 4 h plus 12 h reperfusion. Transfection with Hsp20 decreased FasL and Bax expression and inhibited caspases 3 and p115 cleavage after 12 h reperfusion following 4 h OGD. (b) Quantitation (mean ± SEM) of (a) from three independent experiments. Values are expressed as mean ± SEM. ∗P < 0.05 compared to N2a Cells treated with OGD 4 h plus 12 h reperfusion. ∗∗P < 0.01 compared to N2a Cells treated with OGD 4 h plus 12 h reperfusion.

Mentions: To determine whether Hsp20 modulated the expression of apoptotic proteins and p115 cleavage, N2a cells were transfected with pEGFP-N1 and pEGFP-Hsp20 and treated with OGD 4 h plus 12 h reperfusion (Figure 5). Western blotting results revealed that FasL expression, caspases 3, and p115 cleavage were significantly increased in N2a Cells transfected with pEGFP-N1 after OGD 4 h plus 12 h reperfusion. However, the enhancement of FasL expression, caspases 3, and p115 cleavage was significantly inhibited in N2a Cells transfected with Hsp20. The increased expression of Bax was also inhibited in N2a cells transfected with Hsp20, though not significantly. Together, these data strongly suggest that increased Hsp20 expression ameliorates OGDR-induced elevation of apoptotic proteins and p115 cleavage.


Hsp20 Protects against Oxygen-Glucose Deprivation/Reperfusion-Induced Golgi Fragmentation and Apoptosis through Fas/FasL Pathway.

Zhong B, Hu Z, Tan J, Lu T, Lei Q, Chen C, Zeng L - Oxid Med Cell Longev (2015)

Hsp20 decreases FasL and Bax expression and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. The experiment was repeated independently for at least three times. (a) Effects of Hsp20 on apoptotic proteins expression and p115 cleavage in N2a Cells treated with OGD 4 h plus 12 h reperfusion. Transfection with Hsp20 decreased FasL and Bax expression and inhibited caspases 3 and p115 cleavage after 12 h reperfusion following 4 h OGD. (b) Quantitation (mean ± SEM) of (a) from three independent experiments. Values are expressed as mean ± SEM. ∗P < 0.05 compared to N2a Cells treated with OGD 4 h plus 12 h reperfusion. ∗∗P < 0.01 compared to N2a Cells treated with OGD 4 h plus 12 h reperfusion.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig5: Hsp20 decreases FasL and Bax expression and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. The experiment was repeated independently for at least three times. (a) Effects of Hsp20 on apoptotic proteins expression and p115 cleavage in N2a Cells treated with OGD 4 h plus 12 h reperfusion. Transfection with Hsp20 decreased FasL and Bax expression and inhibited caspases 3 and p115 cleavage after 12 h reperfusion following 4 h OGD. (b) Quantitation (mean ± SEM) of (a) from three independent experiments. Values are expressed as mean ± SEM. ∗P < 0.05 compared to N2a Cells treated with OGD 4 h plus 12 h reperfusion. ∗∗P < 0.01 compared to N2a Cells treated with OGD 4 h plus 12 h reperfusion.
Mentions: To determine whether Hsp20 modulated the expression of apoptotic proteins and p115 cleavage, N2a cells were transfected with pEGFP-N1 and pEGFP-Hsp20 and treated with OGD 4 h plus 12 h reperfusion (Figure 5). Western blotting results revealed that FasL expression, caspases 3, and p115 cleavage were significantly increased in N2a Cells transfected with pEGFP-N1 after OGD 4 h plus 12 h reperfusion. However, the enhancement of FasL expression, caspases 3, and p115 cleavage was significantly inhibited in N2a Cells transfected with Hsp20. The increased expression of Bax was also inhibited in N2a cells transfected with Hsp20, though not significantly. Together, these data strongly suggest that increased Hsp20 expression ameliorates OGDR-induced elevation of apoptotic proteins and p115 cleavage.

Bottom Line: Finding effective neuroprotective agents has become a priority in the treatment of ischemic stroke.However, transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation and apoptosis.Hsp20 interacts with Bax, decreases FasL and Bax expression, and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China ; Department of Traditional Chinese Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.

ABSTRACT
Cerebral ischemia-reperfusion injury plays an important role in the development of tissue injury after acute ischemic stroke. Finding effective neuroprotective agents has become a priority in the treatment of ischemic stroke. The Golgi apparatus (GA) is a pivotal organelle and its protection is an attractive target in the treatment of cerebral ischemia-reperfusion injury. Protective effects of Hsp20, a potential cytoprotective agent due to its chaperone-like activity and involvement in regulation of many vital processes, on GA were assessed in an ischemia-reperfusion injury model. Mouse neuroblastoma Neuro2a (N2a) cells were subjected to oxygen-glucose deprivation/reperfusion (OGDR) insult. OGDR induces Golgi fragmentation, apoptosis, and p115 cleavage in N2a cells. However, transfection with Hsp20 significantly attenuates OGDR-induced Golgi fragmentation and apoptosis. Hsp20 interacts with Bax, decreases FasL and Bax expression, and inhibits caspases 3 and p115 cleavage in N2a cells exposed to OGDR. Our data demonstrate that increased Hsp20 expression protects against OGDR-induced Golgi fragmentation and apoptosis, likely through interaction with Bax and subsequent amelioration of the OGDR-induced elevation in p115 cleavage via the Fas/FasL signaling pathway. This neuroprotective potential of Hsp20 against OGDR insult and the underlying mechanism will pave the way for its potential clinical application for cerebral ischemia-reperfusion related disorders.

No MeSH data available.


Related in: MedlinePlus