Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro

Gabryel, Bożena; Chalimoniuk, Małgorzata; Stolecka, Anna; Waniek, Katarzyna; Langfort, Józef; Małecki, Andrzej

doi:10.1254/jphs.fp0060605

Cited by 24 publications

(12 citation statements)

References 69 publications

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“…Thus increased cPLA 2 would release more AA, which may interrupt the anti-apoptotic action of 14-3-3ζ in the brain. Consistent with these findings, a recent study showed that the inhibition of cPLA 2 -mediated AA release reduced apoptosis in astrocytes (57). Additionally, mood stabilizers are reported to suppress caspase-3 activity, stimulate Bcl-2 and BDNF expression and enhance neurogenesis in rat hippocampus (14–16).…”

Section: Discussionsupporting

confidence: 64%

Altered expression of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients

Kim

Rapoport

Rao

2010

Neurobiology of Disease

181

138

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Bipolar disorder (BD) is a progressive psychiatric disorder characterized by recurrent changes of mood, and is associated with cognitive decline. There is evidence of excitotoxicity, neuroinflammation, upregulated arachidonic acid (AA) cascade signaling and brain atrophy in BD patients. These observations suggest that BD pathology may be associated with apoptosis as well as with disturbed synaptic function. To test this hypothesis, we measured mRNA and protein levels of the pro-apoptotic (Bax, BAD, Caspase-9 and Caspase-3) and anti-apoptotic factors (BDNF and Bcl-2), and of pre-and post-synaptic markers (synaptophysin and drebrin), in postmortem brain from 10 BD patients and 10 age-matched controls. Consistent with the hypothesis, BD brains showed significant increases in protein and mRNA levels of the pro-apoptotic factors and significant decreases of levels of the anti-apoptotic factors and the synaptic markers, synaptophysin and drebrin. These differences may contribute to brain atrophy and progressive cognitive changes in BD.

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Section: Discussionsupporting

confidence: 64%

Altered expression of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients

Kim

Rapoport

Rao

2010

Neurobiology of Disease

181

138

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“…Calcineurin signaling also mediated the activation of the cytoskeletal actin severing protein cofilin and the resulting neuronal death in oxygen-glucose deprivation/reperfusion and chemical induced oxidative stress, to in vitro models of ischemia [34]. Moreover, cyclosporine A prevented the apoptosis of astrocytes exposed to simulated ischemia in vitro via a calcineurin and Erk1/2-dependent mechanism [233] and through the inhibition of cytosolic phospholipase A2- (PLA2-) mediated release of arachidonic acid [234]. …”

Section: Controversial Roles In Nervous System Diseasesmentioning

confidence: 99%

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

Kipanyula

Kimaro

Etet

2016

Journal of Aging Research

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The ongoing epidemics of metabolic diseases and increase in the older population have increased the incidences of neurodegenerative diseases. Evidence from murine and cell line models has implicated calcineurin-nuclear factor of activated T-lymphocytes (NFAT) signaling pathway, a Ca2+/calmodulin-dependent major proinflammatory pathway, in the pathogenesis of these diseases. Neurotoxins such as amyloid-β, tau protein, and α-synuclein trigger abnormal calcineurin/NFAT signaling activities. Additionally increased activities of endogenous regulators of calcineurin like plasma membrane Ca2+-ATPase (PMCA) and regulator of calcineurin 1 (RCAN1) also cause neuronal and glial loss and related functional alterations, in neurodegenerative diseases, psychotic disorders, epilepsy, and traumatic brain and spinal cord injuries. Treatment with calcineurin/NFAT inhibitors induces some degree of neuroprotection and decreased reactive gliosis in the central and peripheral nervous system. In this paper, we summarize and discuss the current understanding of the roles of calcineurin/NFAT signaling in physiology and pathologies of the adult and developing nervous system, with an emphasis on recent reports and cutting-edge findings. Calcineurin/NFAT signaling is known for its critical roles in the developing and adult nervous system. Its role in physiological and pathological processes is still controversial. However, available data suggest that its beneficial and detrimental effects are context-dependent. In view of recent reports calcineurin/NFAT signaling is likely to serve as a potential therapeutic target for neurodegenerative diseases and conditions. This review further highlights the need to characterize better all factors determining the outcome of calcineurin/NFAT signaling in diseases and the downstream targets mediating the beneficial and detrimental effects.

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“…Some research has shown that FK506 ameliorates the functional impairment caused by hypoxic (20) or focal ischemia (19) and following intracerebral hemorrhage (21) due to brain damage. The protective effect of FK506 also has been demonstrated after in vitro ischemia (22) and thrombotic ischemia stroke (23). However, there are no data about the effect of FK506 on functional recovery after transient global brain ischemia.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective Treatment With FK506 Reduces Hippocampal Damage and Prevents Learning and Memory Deficits After Transient Global Ischemia in Rat

et al. 2013

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Background:Behavioral studies on animals demonstrated that hippocampal damage could produce learning and memory impairments particularly spatial learning. It has been shown that ischemic damage restricted to only 50% of the CA1 cells of the hippocampus exceed the threshold for production of a behavioral impairment. Objectives: In this study we seek to evaluate the effect of FK506 (tacrolimus) on spatial learning of rats subjected to 20-min global transient ischemia/reperfusion. Material and Methods: In treatment group 2, FK506 (1mg/kg) was given intravenously (IV) 20 minutes before ischemia and in treatment group 3 rats were treated with the same dose of tacrolimus (IV) at the beginning of reperfusion. Morris water maze tests were performed 1 week after ischemia for 4 days. Brain tissue proceeded to TUNEL staining. Results: Our data showed; 1) No statistically significant differences were seen between the treatment group 2 and the control (intact) group thus, this suggests that treatment of ischemia with tacrolimus can improve spatial learning and memory. 2) Tacrolimus treatment ameliorated the increase of TUNEL-positive cells induced by cerebral ischemia indicating the neuro-protective properties of FK506. Conclusions: These results suggest that tacrolimus may reduce cognitive impairment and may be a good candidate for treatment of ischemic brain damage.

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Inhibition of Arachidonic Acid Release by Cytosolic Phospholipase A2 Is Involved in the Antiapoptotic Effect of FK506 and Cyclosporin A on Astrocytes Exposed to Simulated Ischemia In Vitro

Cited by 24 publications

References 69 publications

Altered expression of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients

Altered expression of apoptotic factors and synaptic markers in postmortem brain from bipolar disorder patients

The Emerging Roles of the Calcineurin-Nuclear Factor of Activated T-Lymphocytes Pathway in Nervous System Functions and Diseases

Neuroprotective Treatment With FK506 Reduces Hippocampal Damage and Prevents Learning and Memory Deficits After Transient Global Ischemia in Rat

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