Network


Latest external collaboration on country level. Dive into details by clicking on the dots.

Hotspot


Dive into the research topics where Gong-Ping Liu is active.

Publication


Featured researches published by Gong-Ping Liu.


Neurobiology of Aging | 2008

Homocysteine induces tau phosphorylation by inactivating protein phosphatase 2A in rat hippocampus

Chang-E. Zhang; Qing Tian; Wei Wei; Jun-Hua Peng; Gong-Ping Liu; Xin-Wen Zhou; Qun Wang; Dao-Wen Wang; Jian-Zhi Wang

Hyperhomocysteinemia increases the risk of Alzheimers disease (AD), but the mechanism is elusive. Here, we found that high plasma homocysteine induced by vena caudalis injection for 2 weeks could induce AD-like tau hyperphosphorylation at multiple sites in rat brain hippocampus. Homocysteine inhibited the activity of protein phosphatase 2A (PP2A) with a simultaneously increased Leu(309)-demethylation and Tyr(307)-phosphorylation of PP2A catalytic subunit (PP2A(C)). PP2A(C) Leu(309)-demethylation was positively correlated with its Tyr(307)-phosphorylation; and the abnormally modified PP2A(C) was incompetent in binding to its regulatory subunit (PP2A(B)). Homocysteine also activated methylesterase which stimulates demethylation of PP2A(C). In hippocampal slices of the homocysteine injected-rats and of the AD patients, the demethylated but not the methylated PP2A(C) was co-localized with the hyperphosphorylated tau. A simultaneous supplement of folate and vitamin B12 restored partially the plasma homocysteine level and thus significantly antagonized the homocysteine-induced tau hyperphosphorylation and as well as PP2A inactivation and the activity-related modifications of PP2A(C). These results suggest that homocysteine may be an upstream effector to induce AD-like tau hyperphosphorylation through inactivating PP2A.


American Journal of Pathology | 2009

Hyperhomocysteinemia Increases β-Amyloid by Enhancing Expression of γ-Secretase and Phosphorylation of Amyloid Precursor Protein in Rat Brain

Chang-E. Zhang; Wei Wei; Ying-Hua Liu; Jun-Hua Peng; Qing Tian; Gong-Ping Liu; Yao Zhang; Jian-Zhi Wang

Hyperhomocysteinemia and beta-amyloid (Abeta) overproduction are critical etiological and pathological factors in Alzheimer disease, respectively; however, the intrinsic link between them is still missing. Here, we found that Abeta levels increased and amyloid precursor protein (APP) levels simultaneously decreased in hyperhomocysteinemic rats after a 2-week induction by vena caudalis injection of homocysteine. Concurrently, both the mRNA and protein levels of presenilin-1, a component of gamma-secretase, were elevated, whereas the expression levels of beta-secretase and presenilin-2 were not altered. We also observed that levels of phosphorylated APP at threonine-668, a crucial site facilitating the amyloidogenic cleavage of APP, increased in rats with hyperhomocysteinemia, although the phosphorylation per se did not increase the binding capacity of pT668-APP to the secretases. The enhanced phosphorylation of APP in these rats was not relevant to either c-Jun N-terminal kinase or cyclin-dependent kinase-5. A prominent spatial memory deficit was detected in rats with hyperhomocysteinemia. Simultaneous supplementation of folate and vitamin-B12 attenuated the hyperhomocysteinemia-induced abnormal processing of APP and improved memory. Our data revealed that hyperhomocysteinemia could increase Abeta production through the enhanced expression of gamma-secretase and APP phosphorylation, causing memory deficits that could be rescued by folate and vitamin-B12 treatment in these rats. It is suggested that hyperhomocysteinemia may serve as an upstream factor for increased Abeta production as seen in patients with Alzheimer disease.


Neurobiology of Aging | 2009

Proteasome inhibition increases tau accumulation independent of phosphorylation

Ying-Hua Liu; Wei Wei; Jun Yin; Gong-Ping Liu; Qun Wang; Fu-Yuan Cao; Jian-Zhi Wang

An intrinsic link between proteasome and tau degradation in Alzheimers disease (AD) has been suggested, however, the role of proteasome in the proteolysis of tau is still uncertain. Here, we investigated the influence of proteasome inhibition on the accumulation, phosphorylation, ubiquitination, solubility of tau and the memory retention in rats. We observed that lactacystin inhibited the proteasome activities and increased the level and insolubility of different tau species, including phosphorylated tau. The elevation of the phosphorylated tau was no longer present and the level of pS214 and pT231 tau was even lower than normal level after normalized to total tau. Inhibition of proteasome resulted in activation of cAMP-dependent protein kinase, glycogen synthase kinases-3beta and cyclin-dependent kinase-5, and inhibition of protein phosphatase-2A and c-Jun N-terminal kinase (JNK). Proteasome inhibition did not affect the memory retention of the rats. We conclude that proteasome inhibition increases accumulation and insolubility of tau proteins independent of tau phosphorylation, and JNK inhibition may be partially responsible for the relatively decreased phosphorylation of tau in the rat brains.


Biochemical Journal | 2011

Glycogen synthase kinase-3β regulates Tyr307 phosphorylation of protein phosphatase-2A via protein tyrosine phosphatase 1B but not Src.

Xiu-Qing Yao; Xiao-Xue Zhang; Yang-Yang Yin; Bin Liu; Dan-Ju Luo; Dan Liu; Ning-Ning Chen; Zhong-Fei Ni; Xiong Wang; Qun Wang; Jian-Zhi Wang; Gong-Ping Liu

GSK-3β (glycogen synthase kinase-3β), a crucial tau kinase, negatively regulates PP2A (protein phosphatase 2A), the most active tau phosphatase that is suppressed in the brain in AD (Alzheimers disease). However, the molecular mechanism is not understood. In the present study we found that activation of GSK-3β stimulates the inhibitory phosphorylation of PP2A at Tyr307 (pY307-PP2A), whereas inhibition of GSK-3β decreased the level of pY307-PP2A both in vitro and in vivo. GSK-3β is a serine/threonine kinase that can not phosphorylate tyrosine directly, therefore we measured PTP1B (protein tyrosine phosphatase 1B) and Src (a tyrosine kinase) activities. We found that GSK-3β can modulate both PTP1B and Src protein levels, but it only inhibits PTP1B activity, with no effect on Src. Furthermore, only knockdown of PTP1B but not Src by siRNA (small interfering RNA) eliminates the effects of GSK-3β on PP2A. GSK-3β phosphorylates PTP1B at serine residues, and activation of GSK-3β reduces the mRNA level of PTP1B. Additionally, we also observed that GSK-3 negatively regulates the protein and mRNA levels of PP2A, and knockdown of CREB (cAMP-response-element-binding protein) abolishes the increase in PP2A induced by GSK-3 inhibition. The results of the present study suggest that GSK-3β inhibits PP2A by increasing the inhibitory Tyr307 phosphorylation and decreasing the expression of PP2A, and the mechanism involves inhibition of PTP1B and CREB.


Neurobiology of Aging | 2012

I2PP2A regulates p53 and Akt correlatively and leads the neurons to abort apoptosis

Gong-Ping Liu; Wei Wei; Xin Zhou; Yao Zhang; Hai-Hong Shi; Jun Yin; Xiu-Qing Yao; Cai-Xia Peng; Juan Hu; Qun Wang; Hong-Lian Li; Jian-Zhi Wang

A chronic neuron loss is the cardinal pathology in Alzheimer disease (AD), but it is still not understood why most neurons in AD brain do not accomplish apoptosis even though they are actually exposed to an environment with enriched proapoptotic factors. Protein phosphatase-2A inhibitor-2 (I(2)(PP2A)), an endogenous PP2A inhibitor, is significantly increased in AD brain, but the role of I(2)(PP2A) in AD-like neuron loss is elusive. Here, we show that I(2)(PP2A) regulates p53 and Akt correlatively. The mechanisms involve activated transcription and p38 MAPK activities. More importantly, we demonstrate that the simultaneous activation of Akt induced by I(2)(PP2A) counteracts the hyperactivated p53-induced cell apoptosis. Furthermore, I(2)(PP2A), p53 and Akt are all elevated in the brain of mouse model and AD patients. Our results suggest that the increased I(2)(PP2A) may trigger apoptosis by p53 upregulation, but due to simultaneous activation of Akt, the neurons are aborted from the apoptotic pathway. This finding contributes to the understanding of why most neurons in AD brain do not undergo apoptosis.


Neurodegenerative Diseases | 2014

Hypoxia-Induced Tau Phosphorylation and Memory Deficit in Rats

Chang-E. Zhang; Xifei Yang; Lingyun Li; Xiaojing Sui; Qing Tian; Wei Wei; Jian-Zhi Wang; Gong-Ping Liu

Hypoxia was shown to be associated with an increased risk of Alzheimers disease (AD). The effects of hypoxia on the development of AD pathology and spatial memory ability and the possible molecular mechanisms remain poorly understood. In this study, we demonstrate that rats exposed to a hypoxic condition (10% oxygen concentration) for 1, 2, 4 and 8 weeks (6 h each day) displayed spatial memory impairment and increased tau phosphorylation at Ser198/199/202, Thr205, Ser262, Ser396 and Ser404 in the hippocampus. Concomitantly, the levels of Tyr216-phosphorylated glycogen synthase kinase (GSK)-3β (activated form of GSK-3β) and Tyr307-phosphorylated protein phosphatase 2A (inactivated form of PP2A) were significantly increased in the hippocampus of the rats with 1, 2, 4 and 8 weeks of hypoxia exposure, while the levels of methylated PP2A (activated form of PP2A) were significantly decreased in the hippocampus of the rats with 4 and 8 weeks of hypoxia exposure. In addition, the content of malondialdehyde, an indicator of oxidative stress, was elevated, whereas the activity of superoxide dismutase was not significantly changed in the hippocampus of the rats exposed to hypoxia. Taken together, these data demonstrated that hypoxia induced tau hyperphosphorylation and memory impairment in rats, and that the increased tau phosphorylation could be attributed to activation of GSK-3β and inactivation of PP2A. These data suggest that interventions to improve hypoxia may be helpful to prevent the development of AD pathology and cognitive impairment.


Journal of Alzheimer's Disease | 2011

Folate/vitamin-B12 prevents chronic hyperhomocysteinemia-induced tau hyperphosphorylation and memory deficits in aged rats.

Wei Wei; Ying-Hua Liu; Chang-E. Zhang; Qun Wang; Zelan Wei; Darrell D. Mousseau; Jian-Zhi Wang; Qing Tian; Gong-Ping Liu

Hyperhomocysteinemia is associated with an increased risk of Alzheimers disease (AD). Our previous work has demonstrated that combined folate and vitamin B12 (vit-B12) supplementation prevents tau hyperphosphorylation and memory deficits induced by acute administration of homocysteine in young rats. Here, we further investigated whether folate/vit-B12 supplementation is also effective in aged rats with a chronically high level of homocysteine. 18-month-old rats were injected with homocysteine via the vena caudalis with or without a concurrent folate/vit-B12 supplementation for 28 weeks. We found that hyperhomocysteinemia induced tau hyperphosphorylation and accumulation in hippocampus and cortex. Concurrent signaling changes included the activation of glycogen synthase kinases-3β, cyclin-dependent kinase-5, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38MAPK, and inhibition of protein phosphatase 2A. Although the ability to learn was not affected, the aged rats exhibited significant memory deficits. Folate/vit-B12 supplementation attenuated these biochemical and behavioral correlates. These data demonstrate that folate/vit-B12 supplementation is also effective in a chronic hyperhomocysteinemia model in reversing the AD-like tau pathologies and memory deficits.


Glia | 2012

Upregulation of astrocytes protein phosphatase-2A stimulates astrocytes migration via inhibiting p38 MAPK in tg2576 mice.

Xiu-Ping Liu; Hong-Yun Zheng; Min Qu; Yao Zhang; Fu-Yuan Cao; Qun Wang; Dan Ke; Gong-Ping Liu; Jian-Zhi Wang

One of the earliest neuropathological changes in Alzheimer disease (AD) is the accumulation of astrocytes at sites of β‐amyloid (Aβ) deposits, but the cause of this cellular response is unclear. As the activity of protein phosphatase 2A (PP2A) is significantly decreased in the AD brains, we studied the role of PP2A in astrocytes migration. We observed unexpectedly that PP2A activity associated with glial fibrillary acidic protein, an astrocyte marker, was significantly upregulated in tg2576 mice, demonstrated by an increased enzyme activity, a decreased demethylation at leucine‐309 (DM‐PP2Ac), and a decreased phosphorylation at tyrosine‐307 of PP2A (pY307‐PP2Ac). Further studies by using in vitro wound‐healing model and transwell assay demonstrated that upregulation of PP2A pharmacologically and genetically could stimulate astrocytes migration. Activation of PP2A promotes actin organization and inhibits p38 mitogen‐activated protein kinases (p38 MAPK), while simultaneous activation of p38 MAPK partially abolishes the PP2A‐induced astrocytes migration. Our data suggest that activation of astrocytes PP2A in tg2567 mice may stimulate the migration of astrocytes to the amyloid plaques by p38 MAPK inhibition, implying that PP2A deficits observed in AD may cause Aβ accumulation via hindering the astrocytes migration.


Oncotarget | 2016

Tau accumulation impairs mitophagy via increasing mitochondrial membrane potential and reducing mitochondrial Parkin

Yu Hu; Xia-Chun Li; Zhi-Hao Wang; Yu Luo; Xiangnan Zhang; Xiu-Ping Liu; Qiong Feng; Qun Wang; Zhenyu Yue; Zhong Chen; Keqiang Ye; Jian-Zhi Wang; Gong-Ping Liu

Intracellular accumulation of wild type tau is a hallmark of sporadic Alzheimers disease (AD). However, the molecular mechanisms underlying tau toxicity is not fully understood. Here, we detected mitophagy deficits evidenced by the increased levels of mitophagy markers, including COX IV, TOMM20, and the ratio of mtDNA to genomic DNA indexed as mt-Atp6/Rpl13, in the AD brains and in the human wild type full-length tau (htau) transgenic mice. More interestingly, the mitophagy deficit was only shown in the AD patients who had an increased total tau level. Further studies demonstrated that overexpression of htau induced mitophagy deficits in HEK293 cells, the primary hippocampal neurons and in the brains of C57 mice. Upon overexpression of htau, the mitochondrial membrane potential was increased and the levels of PTEN-induced kinase 1 (PINK1) and Parkin decreased in the mitochondrial fraction, while upregulation of Parkin attenuated the htau-induced mitophagy deficits. Finally, we detected a dose-dependent allocation of tau proteins into the mitochondrial outer membrane fraction along with its cytoplasmic accumulation. These data suggest that intracellular accumulation of htau induces mitophagy deficits by direct inserting into the mitochondrial membrane and thus increasing the membrane potential, which impairs the mitochondrial residence of PINK1/Parkin. Our findings reveal a novel mechanism underlying the htau-induced neuronal toxicities in AD and other tauopathies.


Molecular Neurobiology | 2017

Long-term Ameliorative Effects of the Antidepressant Fluoxetine Exposure on Cognitive Deficits in 3 × TgAD Mice

Li Jin; Lifeng Gao; Dong-Sheng Sun; Hao Wu; Qun Wang; Dan Ke; Hao Lei; Jian-Zhi Wang; Gong-Ping Liu

Fluoxetine, a selective serotonin reuptake inhibitor, is neuroprotective; therefore, it has been applied to treat some neurodegenerative disorders. For instance, chronic fluoxetine exposure has short-term effects on Alzheimer’s disease (AD). However, the long-term ameliorative effects of fluoxetine exposure on AD have not been reported. In the present study, 6-month-old 3u2009×u2009TgAD mice were treated with fluoxetine for 15xa0days, and then the influence of fluoxetine was detected at 20xa0days after the drug withdrawal. We found that chronic fluoxetine treatment ameliorated cognitive deficits of 3u2009×u2009TgAD mice and increased the volume of the hippocampal CA1 and dentate gyrus (DG) with increased neuron number and dendritic spine density. Meanwhile, fluoxetine exposure also stimulated the long-term potentiation (LTP) in hippocampal DG. The synaptic-related protein expression increased via activation of the cyclic AMP response element binding (CREB) protein/brain-derived neurotrophic factor (BDNF) signaling pathway induced by fluoxetine exposure. Lastly, we found that fluoxetine treatment decreased beta-amyloid (Aβ) levels. These results further certified that fluoxetine may be a potent effective drug for AD.

Collaboration


Dive into the Gong-Ping Liu's collaboration.

Top Co-Authors

Avatar

Jian-Zhi Wang

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Qun Wang

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Wei Wei

Anhui Medical University

View shared research outputs
Top Co-Authors

Avatar

Chang-E. Zhang

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Dan Ke

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Dong-Sheng Sun

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Qing Tian

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Yu Hu

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Qiong Feng

Huazhong University of Science and Technology

View shared research outputs
Top Co-Authors

Avatar

Yao Zhang

Huazhong University of Science and Technology

View shared research outputs
Researchain Logo
Decentralizing Knowledge