Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal survival in hippocampal cultures

Johnson-Farley, Nadine; Patel, Khushboo; Kim, Deborah; Cowen, David L.

doi:10.1016/j.brainres.2007.04.026

Cited by 63 publications

(44 citation statements)

References 31 publications

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“…In contrast, pretreatment with the ERK inhibitor, U0126, did not have effect on the neuroprotection induced by FGF2. Thus our data revealed that AKT but not ERK signaling pathway was involved in the FGF2 mediated neuroprotection in an AD model, this is consistent with the previous study showing that AKT is required for FGF-2-stimulated survival in primary cultured hippocampal neurons [34]. Since our data did not show significant difference between HMW and LMW FGF2 mediated ERK and AKT activation, the stronger neuroprotective effect induced by HMW FGF2 may be mediated by the other signals.…”

Section: Discussionsupporting

confidence: 92%

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Neuroprotective effects of LMW and HMW FGF2 against amyloid beta toxicity in primary cultured hippocampal neurons

Cheng

Kardami

et al. 2016

Neuroscience Letters

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Basic Fibroblast growth factor (FGF2) is important in development and maintenance of central nervous system function. Studies have demonstrated that low molecular weight (LMW) FGF2 is a neuroprotective factor against various insults in vivo and in vitro. In the present study we investigated the neuroprotective effects of high molecular weight (HMW) and LMW FGF2 against amyloid beta-induced neurotoxicity. The results showed that both LMW and HMW FGF2 attenuated the amyloid beta toxicity in the primary cultured hippocampal neurons as measured by WST and LDH release assay. Moreover, the analysis suggested that HMW FGF2 had stronger neuroprotective effect than LMW FGF2. We then demonstrated that LMW and HMW FGF2 activated the ERK and AKT signaling pathways in a similar way. Furthermore, using the ERK inhibitor and AKT inhibitor, we found that the AKT signaling but not ERK signaling pathway was required for the neuroprotective effects of FGF2. Taken together, these results showed the neuroprotective effects of different forms of FGF2 in an AD model and the mechanism underlying the neuroprotection.

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Section: Discussionsupporting

confidence: 92%

“…It is known that FGF2 can activate ERK and AKT in the primary cultured hippocampal neurons [34]. In addition, both ERK and AKT signaling pathways are well known for the major roles in mediating the neuroprotective actions of neurotrophic factors [20–22].…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective effects of LMW and HMW FGF2 against amyloid beta toxicity in primary cultured hippocampal neurons

Cheng

Kardami

et al. 2016

Neuroscience Letters

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“…60 Interestingly, FGF-2 promotes differentiation of resident cardiac precursors into functional cardiomyocytes, 61 which would seem at odds with maintenance of a proliferative state unless the action of FGF-2 occurs at an early stage of commitment, when limited mitotic activity occurs in concert with lineage specification. FGF-2 stimulates Akt activity that could account for prosurvival and proproliferative effects, [62][63][64] and Akt activation lies upstream from Pim-1 induction in cardiomyocytes. 31 Induction of nucleostemin expression by Pim-1 activity ( Figure 6) is without precedent in the literature and reveals an important mechanistic basis for Pim-1-mediated promotion of proliferation in the myocardium that will require further investigation.…”

Section: Discussionmentioning

confidence: 99%

Myocardial Induction of Nucleostemin in Response to Postnatal Growth and Pathological Challenge

Siddiqi

Gude

Hosoda

et al. 2008

Circulation Research

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Abstract-Stem cell-specific proteins and regulatory pathways that determine self-renewal and differentiation have become of fundamental importance in understanding regenerative and reparative processes in the myocardium. One such regulatory protein, named nucleostemin, has been studied in the context of stem cells and several cancer cell lines, where expression is associated with proliferation and maintenance of a primitive cellular phenotype. We find nucleostemin is present in young myocardium and is also induced following cardiomyopathic injury. Nucleostemin expression in cardiomyocytes is induced by fibroblast growth factor-2 and accumulates in response to Pim-1 kinase activity. Cardiac stem cells also express nucleostemin that is diminished in response to commitment to a differentiated phenotype. Overexpression of nucleostemin in cultured cardiac stem cells increases proliferation while preserving telomere length, providing a mechanistic basis for potential actions of nucleostemin in promotion of cell survival and proliferation as seen in other cell types. (Circ Res. 2008;103:89-97.)Key Words: nucleostemin Ⅲ cardioprotection Ⅲ cardiomyocytes Ⅲ stem cells Ⅲ Pim-1 Ⅲ telomerase C ellular-based myocardial regeneration depends on tightly regulated signaling cascades that control survival and proliferation. In the case of stem cell populations, these signaling pathways have been predominantly defined by decades of study in hematopoietic 1-4 and developmental contexts. [5][6][7] The relatively recent advent of myocardial adult stem cells and their distinctive characteristics has prompted reexamination of the operational definition of "stem cells" and "stemness." 8,9 The traditional view of stem cell behavior as derived from classic lineage studies may not appropriately reflect the biology of stem cells in tissues characterized by slow cellular turnover such as the myocardium. For example, activation of signaling typically associated with regulation of proliferation and survival in stem cells is also observed in combination with partial or fully committed cellular phenotypes following tissue injury. 10 -12 These revelations have prompted dissolution of long-standing assertions related to "stem cell-associated" signaling, now viewed as regulation of tissue repair and regeneration or, in some, cases oncogenic transformation. [13][14][15][16] Nucleostemin is found at high levels in various stem cells and human cancers, 17 where it has been associated with maintenance of proliferation. [17][18][19][20] Expression of nucleostemin drops precipitously during differentiation 21,22 and genetic deletion of nucleostemin results in embryonic lethality at approximately day 4 postcoitum with blastocysts comprised of cells that fail to enter S phase. 23 Similar arrest in G 0 /G 1 phase of cell cycle was observed in HeLa cells if nucleostemin was eliminated by RNA interference. 20 Nucleostemin has been purported to mediate cellular dedifferentiation and regenerative processes in newts. 24 Although the molecular basis of nucleostem...

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“…Several insulin signaling molecules play essential roles in synaptic plasticity [68], suggesting their role in learning and memory. Activation of insulin receptors result in downstream activation of the phosphatidylinositide 3 kinase (PI3)/Akt pathway [69], an important signaling pathway for synaptic plasticity [70]. Akt inactivates GSK-3β by phosphorylation of the serine-9 residue.…”

Section: Stz-induced Kinase Activationmentioning

confidence: 99%

Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer’s Disease (sAD)-Like Pathology

et al. 2015

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Alzheimer's disease (AD) is a neurodegenerative disorder that is remarkably characterized by pathological hallmarks which include amyloid plaques, neurofibrillary tangles, neuronal loss, and progressive cognitive loss. Several well-known genetic mutations which are being used for the development of a transgenic model of AD lead to an early onset familial AD (fAD)-like condition. However, these settings are only reasons for a small percentage of the total AD cases. The large majorities of AD cases are considered as a sporadic in origin and are less influenced by a single mutation of a gene. The etiology of sporadic Alzheimer's disease (sAD) remains unclear, but numerous risk factors have been identified that increase the chance of developing AD. Among these risk factors are insulin desensitization/resistance state, oxidative stress, neuroinflammation, synapse dysfunction, tau hyperphosphorylation, and deposition of Aβ in the brain. Subsequently, these risk factors lead to development of sAD. However, the underlying molecular mechanism is not so clear. Streptozotocin (STZ) produces similar characteristic pathology of sAD such as altered glucose metabolism, insulin signaling, synaptic dysfunction, protein kinases such as protein kinase B/C, glycogen synthase-3β (GSK-3β) activation, tau hyperphosphorylation, Aβ deposition, and neuronal apoptosis. Further, STZ also leads to inhibition of Akt/PKB, insulin receptor (IR) signaling molecule, and insulin resistance in brain. These alterations mediated by STZ can be used to explore the underlying molecular and pathophysiological mechanism of AD (especially sAD) and their therapeutic intervention for drug development against AD pathology.

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Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal survival in hippocampal cultures

Cited by 63 publications

References 31 publications

Neuroprotective effects of LMW and HMW FGF2 against amyloid beta toxicity in primary cultured hippocampal neurons

Neuroprotective effects of LMW and HMW FGF2 against amyloid beta toxicity in primary cultured hippocampal neurons

Myocardial Induction of Nucleostemin in Response to Postnatal Growth and Pathological Challenge

Streptozotocin Intracerebroventricular-Induced Neurotoxicity and Brain Insulin Resistance: a Therapeutic Intervention for Treatment of Sporadic Alzheimer’s Disease (sAD)-Like Pathology

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