Phospholipase A2 in acute pancreatitis: review

Nevalainen, Timo J.

doi:10.1016/j.amjsurg.2007.04.004

Cited by 7 publications

(3 citation statements)

References 47 publications

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“…In this work, using phospholipase A2 (PLA2) bound to the membrane of lipid vesicles, we present the results of studies of the digestion dynamics of single nanometer-scale phospholipid vesicles by single unlabeled phospholipases in a biological fluid as complex as human cerebrospinal fluid (CSF). Concerning the enzyme used in our work, we recall that PLA2 designates the particularly important A2 subclass of phospholipases, which belongs to a large family of hydrolytic enzymes known to catalyze the digestion of phospholipids at the interface of lipid aggregates such as micelles, monolayers, and bilayers. − In particular, PLA2 is responsible for the conversion of glycerophospholipids to lysophospholipids and free fatty acids, with the latter being a critical mediator and precursor in inflammation, for example. , The broad and important biological role of PLA2 becomes apparent from its function as an antimicrobial agent , as well as observations demonstrating that changes in PLA2 activity and/or the expression level correlate with numerous pathological conditions, such as cancer, , acute pancreatitis, and coronary heart diseases and ischemic stroke , plus a broad range of neurodegenerative disorders, such as schizophrenia and Alzheimer’s disease. , Variations in PLA2 activity can accordingly serve as a diagnostic and prognostic disease biomarker, and this and related membrane-associated enzymes have also emerged as potential targets in drug development. , …”

Section: Introductionmentioning

confidence: 99%

Single Lipid Vesicle Assay for Characterizing Single-Enzyme Kinetics of Phospholipid Hydrolysis in a Complex Biological Fluid

et al. 2013

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Imaging of individual lipid vesicles is used to track single-enzyme kinetics of phospholipid hydrolysis. The method is employed to quantify the catalytic activity of phospholipase A2 (PLA2) in both pure and complex biological fluids. The measurements are demonstrated to offer a subpicomolar limit of detection (LOD) of human secretory PLA2 (sPLA2) in up to 1000-fold-diluted cerebrospinal fluid (CSF). An additional new feature provided by the single-enzyme sensitivity is that information about both relative concentration variations of active sPLA2 in CSF and the specific enzymatic activity can be simultaneously obtained. When CSF samples from healthy controls and individuals diagnosed with Alzheimer's disease (AD) are analyzed, the specific enzymatic activity is found to be preserved within 7% in the different CSF samples whereas the enzyme concentration differs by up to 56%. This suggests that the previously reported difference in PLA2 activity in CSF samples from healthy and AD individuals originates from differences in the PLA2 expression level rather than from the enzyme activity. Conventional ensemble averaging methods used to probe sPLA2 activity do not allow one to obtain such information. Together with an improvement in the LOD of at least 1 order of magnitude compared to that of conventional assays, this suggests that the method will become useful in furthering our understanding of the role of PLA2 in health and disease and in detecting the pharmacodynamic effects of PLA2-targeting drug candidates.

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Section: Introductionmentioning

confidence: 99%

Single Lipid Vesicle Assay for Characterizing Single-Enzyme Kinetics of Phospholipid Hydrolysis in a Complex Biological Fluid

et al. 2013

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“…One such family is Phospholipase g2 (Pla2g2) -a family of enzymes with mul ple interac on partners that exhibits great CNV in vertebrate genomes. Pla2g2 are addi onally interes ng in that they possess mul ple func onal roles and have been differen ally neofunc onalized in divergent vertebrate lineages -mammalian Pla2g2A is an important component of innate immunity (Nevalainen 2007;Birts, Barton, and Wilton 2010) , whilst Pla2g2G are a major component of the venom of viperid snakes (Kini 2003) . Pla2g2 is also an excellent candidate for compara ve genomics research because the cluster is located in a region known to be syntenic across vertebrate genomes -in all these genomes, the region of interest is flanked by the OTUD3 and UBXN10 genes (Yamaguchi et al 2014;Dowell et al 2016) .…”

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confidence: 99%

Reconstructing the evolutionary history of a functionally diverse gene family reveals complexity at the genetic origins of novelty

Koludarov

Suranse³

et al. 2019

Preprint

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Gene duplica on is associated with the evolu on of many novel biological func ons at the molecular level. The dominant view, o en referred to as "neofunc onaliza on", is that duplica ons precede many novel gene func ons by crea ng func onally redundant copies which are less constrained than singletons. Numerous alterna ve models have been formulated, however, including several (such as "subfunc onaliza on" and "escape from adap ve constraints") in which novel func ons emerge prior to duplica on. Unfortunately, few studies have reconstructed the evolu onary history of a func onally diverse gene family sufficiently well to differen ate between these models. In order to understand how gene families evolve and to what extent they fit par cular evolu onary models, here we examined the evolu on of the g2 family of phospholipase A2 in 92 genomes from all major lineages of Vertebrata. This family is evolu onarily important and has been co-opted for a diverse range of func ons, including innate immunity and venom. The genomic region in which this family is located is remarkably syntenic. This allowed us to reconstruct all duplica on events over hundreds of millions of years of evolu onary history using a novel method to annotate gene clusters, which overcomes many limita ons of automa c annota on. Surprisingly, we found that even at this level of resolu on our data could not be unambiguously fit to exis ng models of gene family evolu on. This suggests that each model may describe a part-truth that doesn't capture the full complexity of gene family evolu on. Graphical abstract Introduc onPerhaps the most important goal in evolu onary biology remains the explana on of the origins of novelty -how do new func ons, traits, and ul mately organisms arise? Gene duplica on is widely considered one of the most important mechanisms facilita ng the evolu on of novel func ons (Ohno 1970;Innan and Kondrashov 2010) . However, duplica on itself is o en treated as a "black box" -a form of "random" muta on -and numerous apparently contradictory models have been ar culated to explain the fates of duplicate genes (Conant and Wolfe 2008;Innan and Kondrashov 2010) . Although discussion of duplica on and redundancy arguably goes back to Darwin (who had no knowledge of genes and spoke of redundant "organs") and has a rich history in the 20th Century (Taylor and Raes 2004) , the "neofunc onaliza on" model of Susumu Ohno has loomed large in the field of molecular evolu on since the publica on of the seminal text "Evolu on by Gene Duplica on" in 1970 (Ohno 1970) . Briefly, this model describes gene duplica on (a neutral process) facilita ng the genesis of novelty by crea ng func onally redundant gene copies which, no longer constrained by the func onal role of the molecule encoded by the "parent" gene, enjoy a period of relaxed selec on in which neutral muta ons may accumulate. Any poten ally beneficial muta ons acquired during this period of neutral change may then be fixed by posi ve selec on.

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“…It has been reported that the membranes of cells undergoing apoptosis are highly susceptible to type II sPLA 2 [48]. The plasma membranes of cells elicited by proinflammatory stimuli or microvesicles shed from activated cells are sensitive to extracellular type II sPLA 2 that liberates fatty acids and lysophospholipids, both potent membrane-perturbing agents which may cause damage to cells [25,49,50]. Our findings demonstrated that apoptotic nucleus with chromatin condensation, chromatin margination, and loss of the nuclear membrane integrity was proved under electron microscope.…”

Section: Discussionmentioning

confidence: 99%

Changes of Inflammation and Apoptosis in Adrenal Gland After Experimental Injury in Rats with Acute Necrotizing Pancreatitis

Wang

et al. 2010

Inflammation

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We hypothesize that adrenal insufficiency in acute necrotizing pancreatitis (ANP) is attributable to hemorrhagic inflammation, necrosis, and apoptosis of the adrenal cortex. Arguments to support this view are presented in the study that investigated morphological and functional changes of adrenal and the distinct roles of inflammatory mediator secretory phospholipase A(2) (sPLA(2)) and apoptosis-related genes Bax and Bcl-2 played in acute adrenal injury in ANP. After ANP model was induced, pancreatic histology, serum amylase, sPLA(2), and corticosterone were analyzed. The adrenal morphology, apoptotic cells by TUNEL assay, and ultrastructures were observed. sPLA(2)-IIA and Bcl-2 and Bax expressions were detected by immunohistochemistry. Histopathologic grading of adrenal was higher in ANP group than in controls. Serum corticosterone was stimulated to maximal level at 3 h, then dropped to the bottom at 24 h (P<0.05). Apoptotic index, sPLA2-IIA, and Bax expression were increased steeply after pancreatitis, and the Bax/Bcl-2 ratio was elevated gradually (P<0.05). Sustained decrease in serum corticosterone level following adrenal injury during ANP appears to be, in part, due to the crucial roles of inflammation and apoptosis in adrenal cortex. These findings could suggest that sPLA2, Bax, and Bcl-2 may be involved in the course of adrenal injury after ANP.

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Phospholipase A2 in acute pancreatitis: review

Cited by 7 publications

References 47 publications

Single Lipid Vesicle Assay for Characterizing Single-Enzyme Kinetics of Phospholipid Hydrolysis in a Complex Biological Fluid

Single Lipid Vesicle Assay for Characterizing Single-Enzyme Kinetics of Phospholipid Hydrolysis in a Complex Biological Fluid

Reconstructing the evolutionary history of a functionally diverse gene family reveals complexity at the genetic origins of novelty

Changes of Inflammation and Apoptosis in Adrenal Gland After Experimental Injury in Rats with Acute Necrotizing Pancreatitis

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