bFGF inhibits ER stress induced by ischemic oxidative injury via activation of the PI3K/Akt and ERK1/2 pathways

Wang, Zhouguang; Zhang, Hongyu; Xu, Xin; Shi, Hongxue; Yu, Xiang; Wang, Xiaojie; Yan, Yongbo; Fu, Xiaobing; Hu, Houwen; Li, Xiaokun; Xiao, Jian

doi:10.1016/j.toxlet.2012.05.006

Cited by 98 publications

(71 citation statements)

References 59 publications

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“…However, the mechanism underlying the SO 2 -mediated activation of the PI3K-Akt signaling pathway is not clear. Previous studies indicated that SO 2 could increase oxidative stress in myocardial tissues [26] , and the over-production of oxidants upregulated the PI3K-Akt signaling path way [27,28] . Therefore, SO 2 may have activated the PI3K-Akt signaling pathway by stimulating the oxidative response.…”

Section: Discussionmentioning

confidence: 96%

The PI3K/Akt pathway mediates the protection of SO2 preconditioning against myocardial ischemia/reperfusion injury in rats

Zhao¹,

Yang²,

Wang³

et al. 2013

Acta Pharmacol Sin

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Aim: To explore the mechanisms underlying the protection by SO 2 preconditioning against rat myocardial ischemia/reperfusion (I/R) injury. Methods: Male Wistar rats underwent 30-min left coronary artery ligation followed by 120-min reperfusion. An SO 2 donor (1 μmol/kg) was intravenously injected 10 min before the ischemia, while LY294002 (0.3 mg/kg) was intravenously injected 30 min before the ischemia. Plasma activities of LDH and CK were measured with an automatic enzyme analyzer. Myocardial infarct size was detected using Evans-TTC method. The activities of caspase-3 and -9 in myocardium were assayed using a commercial kit, and the levels of p-Akt, Akt, PI3K and p-PI3K were examined with Western blotting. Results: Pretreatment with SO 2 significantly reduced the myocardial infarct size and plasma LDH and CK activities, as well as myocardial caspase-3 and -9 activities in the rats. Furthermore, the pretreatment significantly increased the expression levels of myocardial p-Akt and p-PI3K p85. Administration of the PI3K inhibitor LY294002 blocked all the effects induced by SO 2 pretreatment. Conclusion:The results suggest that the PI3K/Akt pathway mediates the protective effects of SO 2 preconditioning against myocardial I/R injury in rats.

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Section: Discussionmentioning

confidence: 96%

The PI3K/Akt pathway mediates the protection of SO2 preconditioning against myocardial ischemia/reperfusion injury in rats

Zhao¹,

Yang²,

Wang³

et al. 2013

Acta Pharmacol Sin

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“…Three weeks after the first bFGF administration, six rats were selected from each group, their striata were quickly dissected and placed on ice immediately after euthanasia, and immunohistochemistry was performed as described previously [12,13]. Briefly, the rats were anesthetized with 4% choral hydrate (10 ml/kg, intraperitoneal, IP) and then perfused with 4% paraformaldehyde in a 0.1 M phosphate buffer.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…Brain tissues and primary hippocampal neurons were homogenized in lysis buffer as described previously [13]. The cultured cells were lysed in a protein extraction reagent with protease and phosphatase inhibitors.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Another group showed that bFGF protects against rotenone-induced dopaminergic cell death [11]. In our previous study, we found that bFGF inhibits ER stress-induced neuronal cell apoptosis in spinal cord injury and brain ischemia/reperfusion injury [12,13]. Hence, inhibition of ER stress as an underlying mechanism of bFGF for treatment of PD requires further investigation.…”

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confidence: 95%

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Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson’s Disease Model

Cai¹,

Ye²,

Zhu³

et al. 2016

Aging and disease

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Parkinson's disease (PD) is a progressive neurodegenerative disorder with complicated pathophysiologic mechanisms. Endoplasmic reticulum (ER) stress appears to play a critical role in the progression of PD. We demonstrated that basic fibroblast growth factor (bFGF), as a neurotropic factor, inhibited ER stress-induced neuronal cell apoptosis and that 6-hydroxydopamine (6-OHDA)-induced ER stress was involved in the progression of PD in rats. bFGF administration improved motor function recovery, increased tyrosine hydroxylase (TH)-positive neuron survival, and upregulated the levels of neurotransmitters in PD rats. The 6-OHDA-induced ER stress response proteins were inhibited by bFGF treatment. Meanwhile, bFGF also increased expression of TH. The administration of bFGF activated the downstream signals PI3K/Akt and Erk1/2 in vivo and in vitro. Inhibition of the PI3K/Akt and Erk1/2 pathways by specific inhibitors partially reduced the protective effect of bFGF. This study provides new insight towards bFGF translational drug development for PD involving the regulation of ER stress.

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“…Particularly, constitutive activation of the MEK/ERK pathway is reported as a common cause for resistance of melanoma cells to apoptosis mediated by the death receptor and mitochondrial apoptotic pathways (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis

et al. 2016

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Abstract. Accumulation of unfolded proteins in the endoplasmic reticulum (ER) induces ER stress which is observed in many human diseases, including breast cancer. Cellular adaptation to ER stress is mediated by the unfolded protein response (UPR), which aims at restoring ER homeostasis. Higher levels of GRP78 expression indicates constitutive activation of the UPR in breast cancer leading to breast cancer cells that are relatively resistant to ER stress-induced apoptosis. Tunicamycin (TM), an ER stress inducer, constitutively activates the mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK), and (MEK)/ERK pathway which plays a role in upregulation of GRP78 by ER stress in that inhibition of MEK by U0126 reduces the levels of GRP78 and blocks its upregulation by TM. Inhibition of the MEK/ERK pathway by U0126 sensitizes breast cancer cells to TM-induced apoptosis. Inhibition of GRP78 by siRNA knockdown enhances TM-and U0126-induced apoptosis in breast cancer cells. This sensitization of breast cancer cells to TM-induced apoptosis by inhibition of MEK/ERK and GRP78 is caspase-dependent, at least in part, by activation of caspase-4. These results seem to indicate that GRP78 has potential as a chemotherapeutical target and have important implications for new treatment strategies in breast cancer by combination with agents that induce ER stress with inhibitors of the MEK/ERK pathway.

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bFGF inhibits ER stress induced by ischemic oxidative injury via activation of the PI3K/Akt and ERK1/2 pathways

Cited by 98 publications

References 59 publications

The PI3K/Akt pathway mediates the protection of SO2 preconditioning against myocardial ischemia/reperfusion injury in rats

The PI3K/Akt pathway mediates the protection of SO2 preconditioning against myocardial ischemia/reperfusion injury in rats

Inhibition of Endoplasmic Reticulum Stress is Involved in the Neuroprotective Effect of bFGF in the 6-OHDA-Induced Parkinson’s Disease Model

Inhibition of mitogen-activated protein kinase signaling pathway sensitizes breast cancer cells to endoplasmic reticulum stress-induced apoptosis

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