Alteration of second messengers during acute cerebral ischemia – adenylate cyclase, cyclic AMP-dependent protein kinase, and cyclic AMP response element binding protein

Tanaka, Kortaro

doi:10.1016/s0301-0082(01)00002-8

Cited by 109 publications

(78 citation statements)

References 197 publications

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“…63 Finally, our finding that sPIF targets PKA/PKC is particularly intriguing as studies have pointed to the modulation of PKA/ PKC signaling as a therapeutic approach for adult neuronal injury such as Alzheimer's Disease and cerebral ischemic/ stroke. 20,64,65 Importantly, in our previous studies we have demonstrated that subcutaneously injected sPIF was able to reach the brain and localize to neuronal cells as assessed using immunofluorescence. 11 Furthermore, in this previous study, we showed that such a dosing regimen was indeed effective in rescuing brain damage in the same rat model used in this current study.…”

Section: Discussionmentioning

confidence: 94%

PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling

et al. 2015

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A synthetic peptide (sPIF) analogous to the mammalian embryo-derived PreImplantation Factor (PIF) enables neuroprotection in rodent models of experimental autoimmune encephalomyelitis and perinatal brain injury. The protective effects have been attributed, in part, to sPIF's ability to inhibit the biogenesis of microRNA let-7, which is released from injured cells during central nervous system (CNS) damage and induces neuronal death. Here, we uncover another novel mechanism of sPIF-mediated neuroprotection. Using a clinically relevant rat newborn brain injury model, we demonstrate that sPIF, when subcutaneously administrated, is able to reduce cell death, reverse neuronal loss and restore proper cortical architecture. We show, both in vivo and in vitro, that sPIF activates cyclic AMP dependent protein kinase (PKA) and calcium-dependent protein kinase (PKC) signaling, leading to increased phosphorylation of major neuroprotective substrates GAP-43, BAD and CREB. Phosphorylated CREB in turn facilitates expression of Gap43, Bdnf and Bcl2 known to have important roles in regulating neuronal growth, survival and remodeling. As is the case in sPIF-mediated let-7 repression, we provide evidence that sPIF-mediated PKA/PKC activation is dependent on TLR4 expression. Thus, we propose that sPIF imparts neuroprotection via multiple mechanisms at multiple levels downstream of TLR4. Given the recent FDA fast-track approval of sPIF for clinical trials, its potential clinical application for treating other CNS diseases can be envisioned.

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Section: Discussionmentioning

confidence: 94%

PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling

et al. 2015

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“…Because it has been previously reported that a link exists between Akt and the transcription factor CREB, 36,37 which might provide potent survival signals during ischemia, [38][39][40][41] we tested if this survival signaling could also be affected by rapamycin. As shown in Figure 6A, p-CREB colocalized with p-Akt, indicating they are both expressed in the same cells after treatment with rapamycin.…”

Section: D)mentioning

confidence: 99%

Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia

Carloni¹,

Girelli²,

Scopa³

et al. 2010

Autophagy

240

180

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We have previously shown that in neonatal rats subjected to hypoxia-ischemia (HI) rapamycin administration increases autophagy, decreases apoptosis and significantly reduces brain damage. After HI, when autophagy is blocked neuronal cells rapidly progress toward necrotic cell death. The present study was undertaken to assess the potential role of activation of autophagic and phosphatidylinositol 3-kinase (PI3K)/Akt kinase pathways in the neuroprotective effect of rapamycin. Rapamycin administration caused a significant reduction of 70 kDa s6 kinase (p70S6K) phosphorylation and a significant increase of the autophagic proteins Beclin 1 and microtubule-associated protein 1 light chain 3 (Lc3), as of monodansylcadaverine (MDC) labeling in the lesioned side. The phosphorylation of Akt and cAMP response element binding protein (CREB) was increased in neuronal cells, and both p-Akt and p-CREB colocalized with Beclin 1. Wortmannin (WM) administration significantly reduced Akt and CREB phosphorylation as well as the neuroprotective effect of rapamycin but did not affect the phosphorylation of p70S6K, the expression of Beclin 1 and LC3, and MDC labeling. In contrast, 3-methyladenine (3MA) reduced the increased Beclin 1 expression, the MDC labeling and the neuroprotective effect of rapamycin without affecting Akt phosphorylation. However, both compounds significantly increased necrotic cell death. Taken together, these data indicate that in neonatal HI autophagy can be part of an integrated prosurvival signaling which includes the PI3K-Akt-mammalian target of rapamycin (mTOR) axis. When the autophagic or the PI3K-Akt-mTOR pathways are interrupted cells undergo necrotic cell death. © 2010 Landes Bioscience

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“…Protein kinase A and PKC are important signaling molecules in a variety of cellular functions, including modulation of neurotransmitter release, regulation of ion channels and enzymes, control of growth and differentiation, and modification of neuronal plasticity (Majewski and Iannazzo, 1998;Leenders and Sheng, 2005). In addition to involvement in normal physiologic events, these two kinases have also been shown to play an important role in d-opioid receptor and extracellular K + D Chao et al pathophysiologic events such as response to hypoxia/ischemia (Tanaka, 2001;Selvatici et al, 2002;Raval et al, 2003;Libien et al, 2005). Our previous studies and those of others have shown that DOR regulates PKA and PKC activities under certain conditions (Lou and Pei, 1997;Yao et al, 2003;Ma et al, 2005), suggesting an involvement of these protein kinases in DOR signaling.…”

Section: L) (E-h)mentioning

confidence: 99%

Cortical δ-Opioid Receptors Potentiate K⁺ Homeostasis During Anoxia and Oxygen–Glucose Deprivation

Chao

Donnelly

Yin

et al. 2006

J Cereb Blood Flow Metab

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Central neurons are extremely vulnerable to hypoxic/ischemic insult, which is a major cause of neurologic morbidity and mortality as a consequence of neuronal dysfunction and death. Our recent work has shown that d-opioid receptor (DOR) is neuroprotective against hypoxic and excitotoxic stress, although the underlying mechanisms remain unclear. Because hypoxia/ischemia disrupts ionic homeostasis with an increase in extracellular K + , which plays a role in neuronal death, we asked whether DOR activation preserves K + homeostasis during hypoxic/ischemic stress. To test this hypothesis, extracellular recordings with K + -sensitive microelectrodes were performed in mouse cortical slices under anoxia or oxygen-glucose deprivation (OGD). The main findings in this study are that (1) DOR activation with [D-Ala 2 , D-Leu 5 ]-enkephalinamide attenuated the anoxia-and OGD-induced increase in extracellular K + and decrease in DC potential in cortical slices; (2) DOR inhibition with naltrindole, a DOR antagonist, completely abolished the DOR-mediated prevention of increase in extracellular K + and decrease in DC potential; (3) inhibition of protein kinase A (PKA) with N-(2-[p-bromocinnamylamino]-ethyl)-5-isoquinolinesulfonamide dihydrochloride had no effect on the DOR protection; and (4) inhibition of protein kinase C (PKC) with chelerythrine chloride reduced the DOR protection, whereas the PKC activator (phorbol 12-myristate 13-acetate) mimicked the effect of DOR activation on K + homeostasis. These data suggest that activation of DOR protects the cortex against anoxia-or ODG-induced derangement of potassium homeostasis, and this protection occurs via a PKC-dependent and PKA-independent pathway. We conclude that an important aspect of DOR-mediated neuroprotection is its early action against derangement of K + homeostasis during anoxia or ischemia.

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Alteration of second messengers during acute cerebral ischemia – adenylate cyclase, cyclic AMP-dependent protein kinase, and cyclic AMP response element binding protein

Cited by 109 publications

References 197 publications

PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling

PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling

Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia

Cortical δ-Opioid Receptors Potentiate K⁺ Homeostasis During Anoxia and Oxygen–Glucose Deprivation

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Alteration of second messengers during acute cerebral ischemia – adenylate cyclase, cyclic AMP-dependent protein kinase, and cyclic AMP response element binding protein

Cited by 109 publications

References 197 publications

PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling

PreImplantation Factor bolsters neuroprotection via modulating Protein Kinase A and Protein Kinase C signaling

Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia

Cortical δ-Opioid Receptors Potentiate K+ Homeostasis During Anoxia and Oxygen–Glucose Deprivation

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Cortical δ-Opioid Receptors Potentiate K⁺ Homeostasis During Anoxia and Oxygen–Glucose Deprivation