Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme

Yui, Daishi; Nishida, Yoichiro; Nishina, Tomoko; Mogushi, Kaoru; Tajiri, Mio; Ishibashi, Satoru; Ajioka, Itsuki; Ishikawa, Kinya; Mizusawa, Hidehiro; Murayama, Shigeo; Yokota, Takanori

doi:10.1371/journal.pone.0143518

Cited by 16 publications

(11 citation statements)

References 51 publications

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“…IDE downregulation has been implicated in the development of neurodegenerative disorders, specifically Alzheimer’s disease. 46 , 47 In the context of depressive disorders, one hypothesis is that decreased expression of IDE in the brain may lead to increased levels of insulin, which elevates levels of reactive oxygen species and strengthens inhibitory GABAergic synapses. 48 Interestingly, the accumulation of reactive oxygen species has been implicated in a number of psychiatric disorders 49 , 50 and it has been suggested that oxidative stress is a potential biomarker of MDD.…”

Section: Discussionmentioning

confidence: 99%

Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals

Pacis

et al. 2017

Transl Psychiatry

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5-Hydroxymethylcytosine (5hmC) is a recently characterized epigenetic mark that is particularly abundant in brain tissue and that regulates gene transcription. We have recently begun to understand the important role of 5hmC in brain development, plasticity and disease, but there are currently little data on 5hmC alterations in psychiatric illnesses. Here we report what we believe to be the first genome-wide analysis of 5hmC in the depressed brain. Using AbaSI sequencing, we investigated 5hmC in the prefrontal cortex of depressed (N=19) and psychiatrically healthy controls (N=19). Consistent with previous global 5hmC analyses in other phenotypes, and likely owing to the inter-individual variability in 5hmC content, the distribution of 5hmC across chromosomes and genomic features was not different between groups. We did, however, find 550 CpGs with suggestive evidence of differential hydroxymethylation. Of these, we validated CpGs in the gene body of myosin XVI (MYO16) and insulin-degrading enzyme using targeted oxidative bisulfite sequencing. Furthermore, the enrichment of 5hmC was also associated with changes in the expression of these two genes in depressed suicides. Together, our results present a novel mechanism linking increased 5hmC to depression and provide a framework for future research in this field.

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Section: Discussionmentioning

confidence: 99%

Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals

Pacis

et al. 2017

Transl Psychiatry

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“…The IDE gene is located on chromosome 10q23.3 close to a region of linkage for the late-onset Alzheimer's Disease susceptibility genome [79]. A mouse model of AD shows decreased IDE levels in the cerebrum and accelerated phenotypic features of AD [80]. Through immunohistochemical studies, this group also demonstrated that human astrocytic phospholipase A2 group 3 (Pla2g3) expression was significantly increased in human AD brains compared to controls.…”

Section: Clinical Impact Of Insulin Degrading Enzyme (Ide) On Alzheimmentioning

confidence: 95%

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

et al. 2017

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BackgroundAssociation of Alzheimer's Disease (AD) with Type 2 Diabetes (T2D) has been well established. Cyclo(His-Pro) plus zinc (Cyclo-Z) treatment ameliorated diabetes in rats and similar improvements have been seen in human patients. Treatment of amyloid precursor protein (APP) transgenic mice with Cyclo-Z exhibited memory improvements and significantly reduced Aβ-40 and Aβ-42 protein levels in the brain tissues of the mice.Scope of reviewMetabolic relationship between AD and T2D will be described with particular attention to insulin sensitivity and Aβ degradation in brain and plasma tissues. Mechanistic effect of insulin degrading enzyme (IDE) in decreasing blood glucose and brain Aβ levels will be elucidated. Cyclo-Z effects on these biochemical parameters will be discussed.Major conclusionStimulation of IDE synthesis is effective for the clinical treatment of metabolic diseases including AD and T2D.General significanceCyclo-Z might be the effective treatment of AD and T2D by stimulating IDE synthesis.

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“…PLA2 has a number of subfamilies of enzymes, one of which includes secreted PLA2 (sPLA2). sPLA2 exist as ten active isoforms, differing in the source of organisms and sites of activity [ 32 – 36 ]. One isoform; sPLA2-IIA, has been identified as exhibiting sensitivity and specificity of more than 90% towards sepsis [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

CD64 and Group II Secretory Phospholipase A2 (sPLA2-IIA) as Biomarkers for Distinguishing Adult Sepsis and Bacterial Infections in the Emergency Department

et al. 2016

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IntroductionEarly diagnosis of sepsis and bacterial infection is imperative as treatment relies on early antibiotic administration. There is a need to develop new biomarkers to detect patients with sepsis and bacterial infection as early as possible, thereby enabling prompt antibiotic treatment and improving the survival rate.MethodsFifty-one adult patients with suspected bacterial sepsis on admission to the Emergency Department (ED) of a teaching hospital were included into the study. All relevant cultures and serology tests were performed. Serum levels for Group II Secretory Phospholipase A2 (sPLA2-IIA) and CD64 were subsequently analyzed.Results and DiscussionSepsis was confirmed in 42 patients from a total of 51 recruited subjects. Twenty-one patients had culture-confirmed bacterial infections. Both biomarkers were shown to be good in distinguishing sepsis from non-sepsis groups. CD64 and sPLA2-IIA also demonstrated a strong correlation with early sepsis diagnosis in adults. The area under the curve (AUC) of both Receiver Operating Characteristic curves showed that sPLA2-IIA was better than CD64 (AUC = 0.93, 95% confidence interval (CI) = 0.83–0.97 and AUC = 0.88, 95% CI = 0.82–0.99, respectively). The optimum cutoff value was 2.13μg/l for sPLA2-IIA (sensitivity = 91%, specificity = 78%) and 45 antigen bound cell (abc) for CD64 (sensitivity = 81%, specificity = 89%). In diagnosing bacterial infections, sPLA2-IIA showed superiority over CD64 (AUC = 0.97, 95% CI = 0.85–0.96, and AUC = 0.95, 95% CI = 0.93–1.00, respectively). The optimum cutoff value for bacterial infection was 5.63μg/l for sPLA2-IIA (sensitivity = 94%, specificity = 94%) and 46abc for CD64 (sensitivity = 94%, specificity = 83%).ConclusionssPLA2-IIA showed superior performance in sepsis and bacterial infection diagnosis compared to CD64. sPLA2-IIA appears to be an excellent biomarker for sepsis screening and for diagnosing bacterial infections, whereas CD64 could be used for screening bacterial infections. Both biomarkers either alone or in combination with other markers may assist in decision making for early antimicrobial administration. We recommend incorporating sPLA2-IIA and CD64 into the diagnostic algorithm of sepsis in ED.

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Enhanced Phospholipase A2 Group 3 Expression by Oxidative Stress Decreases the Insulin-Degrading Enzyme

Cited by 16 publications

References 51 publications

Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals

Gene-body 5-hydroxymethylation is associated with gene expression changes in the prefrontal cortex of depressed individuals

Metabolic relationship between diabetes and Alzheimer's Disease affected by Cyclo(His-Pro) plus zinc treatment

CD64 and Group II Secretory Phospholipase A2 (sPLA2-IIA) as Biomarkers for Distinguishing Adult Sepsis and Bacterial Infections in the Emergency Department

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