A secretory phospholipase A2-mediated neuroprotection and anti-apoptosis

Armugam, Arunmozhiarasi; Cher, Charmian D.N.; Lim, Kai-Ying; Koh, Dow Rhoon; Howells, David W.; Jeyaseelan, Kandiah

doi:10.1186/1471-2202-10-120

Cited by 23 publications

(20 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a study using a neutral anticoagulant secretory phospholipase A 2 as a neuroprotectant, it has been shown that administration of secretory phospholipase A 2 reduced infarct volume in rats subjected to focal transient cerebral ischemia. Secretory phospholipase A 2 also alleviated the neuronal damage in organotypic hippocampal slices subjected to oxygen glucose deprivation (22). The authors also reported an increase in expression of AQP4 together with several anti-apoptotic and pro-survival genes.…”

Section: Up-regulation Of Aqp1 and Aqp4 Expression In Edema: A Survivalmentioning

confidence: 59%

See 1 more Smart Citation

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

Sepramaniam

Armugam

Lim

et al. 2010

Journal of Biological Chemistry

Self Cite

142

112

View full text Add to dashboard Cite

Aquaporins facilitate efficient diffusion of water across cellular membranes, and water homeostasis is critically important in conditions such as cerebral edema. Changes in aquaporin 1 and 4 expression in the brain are associated with cerebral edema, and the lack of water channel modulators is often highlighted. Here we present evidence of an endogenous modulator of aquaporin 1 and 4. We identify miR-320a as a potential modulator of aquaporin 1 and 4 and explore the possibility of using miR-320a to alter the expression of aquaporin 1 and 4 in normal and ischemic conditions. We show that precursor miR-320a can function as an inhibitor, whereas anti-miR-320a can act as an activator of aquaporin 1 and 4 expressions. We have also shown that antimiR-320a could bring about a reduction of infarct volume in cerebral ischemia with a concomitant increase in aquaporins 1 and 4 mRNA and protein expression. MicroRNAs (miRNAs)2 regulate mRNA expression by binding to the 3Ј-UTR (1). As simple as it sounds, identifying targets for miRNAs remains a challenging task mainly because each miRNA has hundreds of mRNA targets (2). Increasing this complexity are emerging reports on miRNAs binding at 5Ј-UTR as well as promoter regions (3-5). Recent studies also reveal the possibility of miRNAs functioning as transcriptional or splicing regulators within the nucleus (6) and being involved in genetic exchange via exosomes with adjacent cells (7). Because of this complexity in regulation, of the hundreds of miRNAs identified in the human species, only a handful have been assigned their specific targets.Comparison of miRNA profiles between normal and diseased samples allows the identification of crucial miRNAs that are altered during disease conditions and enables one to search for possibilities of altering these expression profiles in an attempt to normalize or reduce the patho-physiological conditions of the disease. Changes in the expression of miRNAs have been reported in several diseases (8 -10) including cerebral ischemia (11-13). Cerebral ischemia is a highly debilitating condition, and ischemia-induced edema further increases complications and morbidity (14). The movement of water into and out of an ischemic brain is thought to be mainly modulated by aquaporins (AQPs), especially aquaporin 1 (AQP1) and aquaporin 4 (AQP4). AQPs are a family of transmembrane proteins involved in transport of water, glycerol, ions, and even CO 2 (15, 16). The 13-member family is ubiquitously expressed in almost all parts of the human body. Often more than one homolog is found to be present in any tissue or organ. In the brain AQP1, 3, 4, 5, 8, and 9 have been reported, with AQP1, 4, and 9 being expressed abundantly (17). The importance of AQP1 and AQP4 regulation in edema has been highlighted in several studies (18,19). AQP4 knockouts in mice showed increased protection against cytotoxic edema caused by water intoxication and permanent focal cerebral ischemia, whereas in conditions leading to vasogenic brain edema, it had a deleterious effect (18,19). s...

show abstract

Section: Up-regulation Of Aqp1 and Aqp4 Expression In Edema: A Survivalmentioning

confidence: 59%

“…For infarct volume quantitation, whole rat brain slices were stained in 2,3,5-triphenyltetrazolium chloride (Sigma) and fixed in 10% buffered formalin. Stained brain slices were scanned, and the images were analyzed using Scion Image analysis software (22).…”

Section: Transient Focal Cerebral Ischemia and Quantitation Ofmentioning

confidence: 99%

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

Sepramaniam

Armugam

Lim

et al. 2010

Journal of Biological Chemistry

Self Cite

142

112

View full text Add to dashboard Cite

show abstract

“…ischemia and inflammation in various organs (21)(22)(23). Also, we do not know whether some of our patients had circulating tumor cells in Table II.…”

Section: Discussionmentioning

confidence: 97%

Whole blood RNA expression profiles in ovarian cancer patients with or without residual tumors after primary cytoreductive surgery

2012

View full text Add to dashboard Cite

Abstract. Significant improvements in the treatment results of ovarian cancer have been achieved during the last decades, but further improvements require additional methods identifying signs of the disease and its biological behavior, preferably by a simple blood test. We hypothesized that peripheral blood leukocytes may express genes that carry such clinical information. Therefore, we studied the relative gene expressions of 168 cancer-and metastasis-specific genes in blood samples from ovarian cancer patients with different prognoses after primary cytoreductive surgery. Total RNA was extracted from whole blood and the relative gene expression profile of 168 genes were analyzed using real-time qPCR assays. Two groups of patients were analyzed; one group with residual tumor mass after primary surgery, and one group where the tumor was macroscopically radically resected, resulting in no visible tumor mass left behind. The group with the remaining tumor mass after surgery showed significantly different gene expression profiles compared to the group with no remaining tumor mass. Differences were noted for the metastasis associated 1 family, member 2 gene (MTA2), the TNF, α-catenin, interleukin 1β, the KiSS-1 metastasis suppressor and the matrix metallo proteinase 10 genes. All genes were downregulated with a fold-change between 1.15 to 1.57; there were no upregulated genes. Thus, a signature of genes involved in metastasis, invasion and inflammation was found to be significantly downregulated in native unstimulated blood leukocytes from ovarian cancer patients with a poor prognosis. Preoperatively it may serve as a guide to the biology of the tumor and postoperatively in the optimization of adjuvant treatment of ovarian cancer patients.

show abstract

“…Animals were sacrificed at 0 hrs, 3 hrs, 6 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs, 120 hrs and 168 hrs following MCAo and the brain samples were sectioned and subjected to infarct volume quantitation as described previously [10]. Infarct volume was measured by the indirect method formulation described by Swansson et al [11] and Lin et al [12].…”

Section: Methodsmentioning

confidence: 99%

microRNAs Involved in Regulating Spontaneous Recovery in Embolic Stroke Model

et al. 2013

Self Cite

View full text Add to dashboard Cite

To date, miRNA expression studies on cerebral ischemia in both human and animal models have focused mainly on acute phase of ischemic stroke. In this study, we present the roles played by microRNAs in the spontaneous recovery phases in cerebral ischemia using rodent stroke models. Brain tissues were harvested at different reperfusion time points ranging from 0–168 hrs after middle cerebral artery occlusion using homologous emboli. MiRNA and mRNA expression profiles were investigated by microarray followed by multiple statistical analysis. Candidate transcripts were also validated by quantitative RT-PCR. Three specific groups of miRNAs were observed among a total of 346 differentially expressed miRNAs. miRNAs, miR-21, -142-3p, -142-5p, and -146a displayed significant upregulation during stroke recovery (48 hrs to 168 hrs) compared with those during acute phases (0 hrs to 24 hrs). On the other hand, an opposite trend was observed in the expression of miR-196a/b/c, -224 and -324-3p. Interestingly, miR-206, -290, -291a-5p and -30c-1*, positively correlated with the infarct sizes, with an initial increase up to 24hrs followed by a gradual decrease from 48 hrs to 168 hrs (R = 0.95). Taken together with the expression levels of corresponding mRNA targets, we have also found that Hedgehog, Notch, Wnt and TGF-β signaling pathways could play significant roles in stroke recovery and especially in neuronal repair.

show abstract

A secretory phospholipase A2-mediated neuroprotection and anti-apoptosis

Cited by 23 publications

References 50 publications

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

MicroRNA 320a Functions as a Novel Endogenous Modulator of Aquaporins 1 and 4 as Well as a Potential Therapeutic Target in Cerebral Ischemia*

Whole blood RNA expression profiles in ovarian cancer patients with or without residual tumors after primary cytoreductive surgery

microRNAs Involved in Regulating Spontaneous Recovery in Embolic Stroke Model

Contact Info

Product

Resources

About