Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK‐3β and CREB through PI3‐K/Akt pathways

Simão, Fabrício; Matté, Aline; Pagnussat, Aline de Souza; Netto, Carlos Alexandre; Salbego, Christianne Gazzana

doi:10.1111/j.1460-9568.2012.08229.x

Cited by 93 publications

(51 citation statements)

References 46 publications

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“…Berberine ameliorates cartilage degeneration in IL-1β-stimulated rat chondrocytes and in a rat model of OA via AKT signaling [29]. It has been reported that AKT signaling is one crucial upstream signaling pathway for CREB expression [37,38]. In this study, we investigated whether LF required the AKT signaling pathway for the activation of CREB.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Lactoferrin Inhibits IL-1β-Induced Chondrocyte Apoptosis Through AKT1-Induced CREB1 Activation

Xue

Tu²,

Ma³

et al. 2015

Cell Physiol Biochem

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Background/Aims: Chondrocyte apoptosis is largely responsible for cartilage degeneration in osteoarthritis (OA). Interleukin-1 beta (IL-1β) is widely used as a chondrocyte apoptosis-inducing agent, while lactoferrin (LF) is an anabolic reagent which has the potential to inhibit chondrocyte apoptosis. We assessed the effects of LF on cartilage degeneration in IL-1β-induced chondrocytes and in a rat model of OA, and explored the potential molecular mechanisms involved. Methods: Human articular chondrocytes (HACs) were treated with IL-1β alone or in combination with LF. MTT and flow cytometric assays were used to detect changes after treatment with LF. Western blotting was used to examine the relevant molecules regulating apoptosis. Results: We found that IL-1β reduced the viability of HACs, whereas 200 μg/mL of LF significantly counteracted the inhibitory effect of IL-1β. LF significantly inhibited IL-1β-induced HAC apoptosis. The protein expression of the apoptotic markers Caspase-3 and PARP was also significantly reduced in the LF treatment group when analyzed by western blotting. Furthermore, we found that LF triggered CREB1 phosphorylation in IL-1β-induced HAC apoptosis through AKT1 signaling. In addition, LF promoted the repair of articular cartilage damage in a rat OA model with elevated p-CREB levels. Conclusions: These studies suggest that LF has an anti-apoptotic effect on IL-1β-induced chondrocytes, and thus may be a promising novel therapeutic agent for OA.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 99%

Lactoferrin Inhibits IL-1β-Induced Chondrocyte Apoptosis Through AKT1-Induced CREB1 Activation

Xue

Tu²,

Ma³

et al. 2015

Cell Physiol Biochem

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“…Several studies showed that resveratrol has the potential to defend neurons against oxidative assaults induced by a spectrum of treatments, including neurotoxins (Wu et al 2013;Renaud et al 2014) and cerebral ischemic injury (Simao et al 2012). Resveratrol plays a protective role in several neurodegenerative diseases, including PD, Alzheimer's disease (AD), and Huntington's disease (Albani et al 2010), as well as against neuroinflammation (Foti Cuzzola et al 2011).…”

mentioning

confidence: 99%

Resveratrol Protects PC12 Cells from High Glucose-Induced Neurotoxicity Via PI3K/Akt/FoxO3a Pathway

Liu

Yuan

et al. 2014

Cell Mol Neurobiol

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Diabetes is known to be associated with neurodegenerative diseases. Resveratrol, a plant-derived polyphenolic compound found in red wine, possesses antioxidant properties. In this study, we aimed to investigate the effects of resveratrol on the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway in mediating high glucose (HG)-induced injuries in neuronal PC12 cells. PC12 cells were exposed to HG to establish a model of HG neurotoxicity. Results showed that pre-treating PC12 cells with resveratrol before exposure to HG led to increased cell viability, decreased apoptotic cells, and reactive oxygen species generation. Western blot analysis showed that HG decreased the phosphorylation of Akt and FoxO3a and led to the nuclear localization of FoxO3a. These effects were significantly alleviated by resveratrol co-treatment. Furthermore, the protective effects of resveratrol were abolished by PI3K/Akt inhibitor LY294002. All these results demonstrate that resveratrol protected the PC12 cells from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway.

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“…An element that directly controls CREB activity and cell survival is the protein kinase AKT. 44,45 We showed here that NO/cGKII directly influenced nuclear AKT localization in E6 and E8 retinal neurons. Interestingly, NO/cGKII-dependent neuronal death or survival was directly associated with an AKT-regulated CREB activation in the nucleus.…”

Section: Discussionmentioning

confidence: 67%

“…[41][42][43] In different neuronal paradigms, AKT-dependent survival may rely on downstream CREB activity in the nucleus. 44,45 Furthermore, it has been reported that NO regulates AKT activation and nuclear translocation via cGKII in retinal neurons. 22 We then decided to evaluate the role played by AKT in CREB phosphorylation regulated by cGKII in the nuclei.…”

Section: Resultsmentioning

confidence: 99%

The nitric oxide-cGKII system relays death and survival signals during embryonic retinal development via AKT-induced CREB1 activation

et al. 2014

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During early neurogenesis, retinal neuronal cells display a conserved differentiation program in vertebrates. Previous studies established that nitric oxide (NO) and cGMP accumulation regulate essential events in retinal physiology. Here we used pharmacological and genetic loss-of-function to investigate the effects of NO and its downstream signaling pathway in the survival of developing avian retinal neurons in vitro and in vivo. Six-day-old (E6) chick retinal cells displayed increased calcium influx and produced higher amounts of NO when compared with E8 cells. L-arginine (substrate for NO biosynthesis) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP; a nitrosothiol NO donor) promoted extensive cell death in E6 retinas, whereas in E8 both substances decreased apoptosis. The effect of NO at both periods was mediated by soluble guanylyl cyclase (sGC) and cGMP-dependent kinase (cGK) activation. In addition, shRNA-mediated cGKII knockdown prevented NO-induced cell death (E6) and cell survival (E8). This, NO-induced cell death or cell survival was not correlated with an early inhibition of retinal cell proliferation. E6 cells also responded differentially from E8 neurons regarding cyclic AMP-responsive element-binding protein (CREB) activation in the retina in vivo. NO strongly decreased nuclear phospho-CREB staining in E6 but it robustly enhanced CREB phosphorylation in the nuclei of E8 neurons, an effect that was completely abrogated by cGKII shRNAs at both embryonic stages. The ability of NO in regulating CREB differentially during retinal development relied on the capacity of cGKII in decreasing (E6) or increasing (E8) nuclear AKT (V-Akt murine thymoma viral oncogene) activation. Accordingly, inhibiting AKT prevented both cGKII shRNA-mediated CREB upregulation in E6 and SNAP-induced CREB activation in E8. Furthermore, shRNAmediated in vivo cGKII or in vitro CREB1 knockdown confirmed that NO/cGKII dualistically regulated the downstream CREB1 pathway and caspase activation in the chick retina to modulate neuronal viability. These data demonstrate that NO-mediated cGKII signaling may function to control the viability of neuronal cells during early retinal development via AKT/CREB1 activity. Cell Death and Differentiation (2014) 21, 915-928; doi:10.1038/cdd.2014.11; published online 14 February 2014The retina is part of the central nervous system (CNS) because of its derivation from the anterior neural tube. Mature retinal tissue is arranged in a laminar structure composed of seven major classes of cells: ganglion, horizontal, amacrine, bipolar, cone and rod photoreceptors and the Mü ller glia. 1 Early retinal tissue is a pseudo-stratified epithelium in which mitotically active neuronal precursor cells are found. Another noteworthy characteristic of vertebrate retinogenesis is the well-established chronology of cell-type generation, with ganglion cells generally being the first cells to be born and the Mü ller glia and bipolar neurons usually the last. Nevertheless, the differentiation periods of different cell type...

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Resveratrol prevents CA1 neurons against ischemic injury by parallel modulation of both GSK‐3β and CREB through PI3‐K/Akt pathways

Cited by 93 publications

References 46 publications

Lactoferrin Inhibits IL-1β-Induced Chondrocyte Apoptosis Through AKT1-Induced CREB1 Activation

Lactoferrin Inhibits IL-1β-Induced Chondrocyte Apoptosis Through AKT1-Induced CREB1 Activation

Resveratrol Protects PC12 Cells from High Glucose-Induced Neurotoxicity Via PI3K/Akt/FoxO3a Pathway

The nitric oxide-cGKII system relays death and survival signals during embryonic retinal development via AKT-induced CREB1 activation

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