The role of Akt (protein kinase B) and protein kinase C in ischemia–reperfusion injury

Zhao, Ethan; Efendizade, Aslan; Cai, Lining; Ding, Yuchuan

doi:10.1080/01616412.2015.1133024

Cited by 45 publications

(28 citation statements)

References 106 publications

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“…The decrease in PKB expression was attributable to oxidative stress and damage to the cell with indications towards apoptosis. PKB phosphorylates BAD a pro-apoptotic member of the Bcl2 family series causing it to dissociate and lose its pro-apoptotic function [31,32]. Therefore, decreased expression of PKB in this study correlates with the oxidative stress revealed via biochemical assays.…”

Section: Discussionmentioning

confidence: 86%

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

et al. 2017

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(2017) Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway, Redox Report, 22:6, 467-477, DOI: 10.1080/13510002.2017 Objectives: Arsenic is a ubiquitous element that is widely distributed in the environment to which man and animals are exposed. Cardiovascular disease is one of the aftermaths of chronic arsenic exposure-related morbidity and mortality. This study sought to investigate the possibility of reversal from arsenic-induced cardio-renal toxicity following exposure and subsequent withdrawal. The study also seeks to understand the mechanism of action of this reversal. Methods: Rats were orally exposed to sodium arsenite at 10, 20 and 40 mg/kg daily for 4 weeks followed by 4 weeks of withdrawal. Results: Exposure to arsenic caused a significant increase in malondialdehyde, H 2 O 2 generation but decrease total thiol and reduced glutathione levels in both cardiac and renal tissues. Furthermore, increases in superoxide dismutase, glutathione-S-transferase and catalase with significant increases in glutathione peroxidase activities were observed in the cardiac tissues. On the contrary, a significant reduction in the renal antioxidant enzyme activity was recorded following exposure. Also, antioxidant defense system did not return to apparent values after arsenic withdrawal. Immunohistochemistry revealed a reduction in the expression of the prosurvival protein-protein kinase B (Akt/PKB) following exposure to arsenic and this was not reversed by withdrawal Discussion: Exposure to arsenic caused cardio-renal toxicity via induction of oxidative stress and down-regulation of Akt/PKB expressions.

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Section: Discussionmentioning

confidence: 86%

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

et al. 2017

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“…A possible scenario is that BZA and E 2 suppress the expression of CTMP (or other negative regulators of Akt), enabling p‐Akt to be activated after ischaemia, thus promoting phosphorylation and inactivation of the downstream targets of Akt implicated in the apoptotic cell death. If the PI3K/Akt pathway plays a neuroprotective role in cerebral ischaemia, the fact that neither BZA, nor E 2 inhibited its activation should be viewed as a positive feature of both ER ligands.…”

Section: Discussionmentioning

confidence: 99%

The selective oestrogen receptor modulator, bazedoxifene, mimics the neuroprotective effect of 17β‐oestradiol in diabetic ischaemic stroke by modulating oestrogen receptor expression and the MAPK/ERK1/2 signalling pathway

Burguete

Jover‐Mengual

López‐Morales

et al. 2019

J Neuroendocrinology

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Because neuroprotection in stroke should be revisited in the era of recanalisation, the present study analysed the potential neuroprotective effect of the selective oestrogen receptor modulator, bazedoxifene acetate (BZA), in an animal model of diabetic ischaemic stroke that mimics thrombectomy combined with adjuvant administration of a putative neuroprotectant. Four weeks after induction of diabetes (40 mg kg -1 streptozotocin, i.p.), male Wistar rats were subjected to transient middle cerebral artery occlusion (intraluminal thread technique, 60 minutes) and assigned to one of three groups treated with either: vehicle, BZA (3 mg kg -1 day -1 , i.p.) or 17β-oestradiol (E 2 ) (100 μg kg -1 day -1 , i.p.). At 24 hours post-ischaemia-reperfusion, brain damage (neurofunctional score, infarct size and apoptosis), expression of oestrogen receptors (ER)α, ERβ and G protein-coupled oestrogen receptor), and activity of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK)1/2 and phosphoinositide 3-kinase/Akt pathways were analysed. At 24 hours after the ischaemic insult, both BZA-and E 2 -treated animals showed lower brain damage in terms of improved neurofunctional condition, decreased infarct size and decreased apoptotic cell death.Ischaemia-reperfusion induced a significant decrease in ERα and ERβ expression without affecting that of G protein-coupled oestrogen receptor, whereas BZA and E 2 reversed such a decrease. The ischaemic insult up-regulated the activity of both the MAPK/ERK1/2 and phosphoinositide 3-kinase/Akt pathways; BZA and E 2 attenuated the increased activity of the ERK1/2 pathway, without affecting that of the Akt pathway. The results of the present study lend further support to the consideration of BZA as an effective and safer alternative overcoming the drawbacks of E 2 with respect to improving diabetic ischaemic stroke outcome after successful reperfusion. K E Y W O R D S 17β-oestradiol, apoptosis, bazedoxifene, diabetes, ischaemic stroke, selective oestrogen receptor modulators How to cite this article: Burguete MC, Jover-Mengual T, López-Morales MA, et al. The selective oestrogen receptor modulator, bazedoxifene, mimics the neuroprotective effect of 17β-oestradiol in diabetic ischaemic stroke by modulating oestrogen receptor expression and the MAPK/ERK1/2 signalling pathway. J Neuroendocrinol. 2019;31:e12751.

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“…Although the exact molecular mechanisms that lead to survival have not been determined completely, it is known that Akt inhibits the activation of death-signalling molecules, such as GSK3 and BAD, or directly affects the nucleus. 36,37 Nonetheless, we did not explore the possibilities of other hormonal changes that could have a positive impact after an insult. Oestrogen and oxytocin levels change in sires.…”

Section: Interaction With the Pups And Dam But Not The Pregnant Femmentioning

confidence: 99%

Fatherhood diminishes the hippocampal damaging action of excitotoxic lesioning in mice

Anagnostou¹,

Morales²

2019

J Neuroendocrinology

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Parental experience imposes neuroplasticity in the hippocampus of females and males. In lactating rat dams, the hippocampus is protected against excitotoxic damage by kainic acid lesioning, although it is still unknown whether paternity can provide such protection to male rodents. To evaluate the protective effects of fatherhood against excitotoxic lesions, we paired male mice with females and co‐housed them until the day of parturition (PPD0), when we randomly assigned them to two groups: (i) the pregnancy group (males housed individually overnight and injected i.c.v. with 100 ng per 1 μL of kainic acid or vehicle on PPD1) and (ii) the sire group (males housed with the dam and pups until PPD8, when injected i.c.v. after evaluation of parental behaviour). Individually housed virgin adult male mice formed the control group. Markers of neurodegeneration (NeuN, Fluoro‐Jade C) and astrogliosis (glial fibrillary acidic protein) were evaluated in fixed cerebral tissue containing the dorsal CA1, CA3 and CA4 hippocampal subfields. The CA1 subfield did not suffer damage in any of the experimental groups. The sire group exhibited less neurodegeneration and astrogliosis in the CA3 and CA4 subfields compared to their respective controls, independently of the expression of parental behaviour. Western blot analysis was conducted for prolactin (PRL), PRL receptor and related intracellular pathways. Monomeric PRL was lower in the hippocampus of sires in the first week postpartum with a parallel rise of a 48‐kDa dimerised isoform compared to virgin controls. The long isoform of PRL receptor did not change, and signal transducer and activator of transcription 5 (STAT5) was not detected in the hippocampus. However, a sustained rise in pAkt, a signalling molecule that participates in cell survival, was observed in the sire group. These results indicate that the hippocampus of sires housed with the dam and pups is less sensitive to neurotoxic injury, which might not be primarily regulated by PRL‐STAT5‐modulated mechanisms.

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The role of Akt (protein kinase B) and protein kinase C in ischemia–reperfusion injury

Cited by 45 publications

References 106 publications

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

Sodium arsenite-induced cardiovascular and renal dysfunction in rat via oxidative stress and protein kinase B (Akt/PKB) signaling pathway

The selective oestrogen receptor modulator, bazedoxifene, mimics the neuroprotective effect of 17β‐oestradiol in diabetic ischaemic stroke by modulating oestrogen receptor expression and the MAPK/ERK1/2 signalling pathway

Fatherhood diminishes the hippocampal damaging action of excitotoxic lesioning in mice

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