Role of phospholipases A2 and C in myocardial ischemic reperfusion injury

1991 ◽  
Vol 260 (3) ◽  
pp. H877-H883 ◽  
Author(s):  
M. R. Prasad ◽  
L. M. Popescu ◽  
I. I. Moraru ◽  
X. K. Liu ◽  
S. Maity ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Ischemic Myocardium ◽  
Lower Amount ◽  
Cellular Injury ◽  
Membrane Phospholipids ◽  
Nonesterified Fatty Acids ◽  
Subcellular Organelles ◽  
Phospholipases A2 ◽  
Rat Hearts

We investigated the role of phospholipase A2 (PLA2) and phospholipase C (PLC) in myocardial phosholipid degradation and cellular injury during reperfusion of ischemic myocardium. For this purpose, isolated rat hearts were perfused with isotopic arachidonic acid to label its membrane phospholipids. Hearts preperfused with antiphospholipase A2 (anti-PLA2) retained a significantly higher amount of radiolabel in phosphatidylcholine and phosphatidylinositol and a corresponding lower amount of radiolabel in lysophosphatidylcholine and nonesterified fatty acids (P less than 0.05) after 30 min of reperfusion following 30 min of normothermic global ischemia compared with hearts preperfused with nonimmune immunoglobulin G. In similar experiments, antiphospholipase C (anti-PLC)-treated hearts were associated with significantly (P less than 0.05) higher radiolabel in all phospholipids and lower radiolabel in diacyglycerol compared with nonimmune immunoglobulin G-treated hearts. Measurement of phospholipase activity in subcellular organelles of these hearts showed decreased PLA2 activity in cytosol, mitochondria, and microsomes of anti-PLA2-treated hearts and decreased PLC activity of microsomes in anti-PLC-treated hearts. Furthermore, both the antiphospholipases attenuated the release of creatine kinase and lactate dehydrogenase into perfusate and increased contractility as well as coronary flow in the reperfused hearts. Results of this study suggest that both PLA2 and PLC are involved in the degradation of phospholipids and cellular injury that occur during reperfusion of ischemic myocardium.

scholarly journals In VitroAnti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A2

2015 ◽  
Vol 83 (6) ◽  
pp. 2453-2465 ◽  
Author(s):  
Carole Guillaume ◽  
Christine Payré ◽  
Ikram Jemel ◽  
Louise Jeammet ◽  
Sofiane Bezzine ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Plasmodium Falciparum ◽  
Critical Role ◽  
Plasma Lipoproteins ◽  
Nonesterified Fatty Acids ◽  
Content Type ◽  
Phospholipases A2

We have previously shown that secreted phospholipases A2(sPLA2s) from animal venoms inhibit thein vitrodevelopment ofPlasmodium falciparum, the agent of malaria. In addition, the inflammatory-type human group IIA (hGIIA) sPLA2circulates at high levels in the serum of malaria patients. However, the role of the different human sPLA2s in host defense againstP. falciparumhas not been investigated. We show here that 4 out of 10 human sPLA2s, namely, hGX, hGIIF, hGIII, and hGV, exhibit potentin vitroanti-Plasmodiumproperties with half-maximal inhibitory concentrations (IC50s) of 2.9 ± 2.4, 10.7 ± 2.1, 16.5 ± 9.7, and 94.2 ± 41.9 nM, respectively. Other human sPLA2s, including hGIIA, are inactive. The inhibition is dependent on sPLA2catalytic activity and primarily due to hydrolysis of plasma lipoproteins from the parasite culture. Accordingly, purified lipoproteins that have been prehydrolyzed by hGX, hGIIF, hGIII, and hGV are more toxic toP. falciparumthan native lipoproteins. However, the total enzymatic activities of human sPLA2s on purified lipoproteins or plasma did not reflect their inhibitory activities onP. falciparum. For instance, hGIIF is 9-fold more toxic than hGV but releases a lower quantity of nonesterified fatty acids (NEFAs). Lipidomic analyses of released NEFAs from lipoproteins demonstrate that sPLA2s with anti-Plasmodiumproperties are those that release polyunsaturated fatty acids (PUFAs), with hGIIF being the most selective enzyme. NEFAs purified from lipoproteins hydrolyzed by hGIIF were more potent at inhibitingP. falciparumthan those from hGV, and PUFA-enriched liposomes hydrolyzed by sPLA2s were highly toxic, demonstrating the critical role of PUFAs. The selectivity of sPLA2s toward low- and high-density (LDL and HDL, respectively) lipoproteins and their ability to directly attack parasitized erythrocytes further explain their anti-Plasmodiumactivity. Together, our findings indicate that 4 human sPLA2s are active againstP. falciparumin vitroand pave the way to future investigations on theirin vivocontribution in malaria pathophysiology.

The Role of Inflammasomes in Atherosclerosis and Stroke Pathogenesis

2020 ◽  
Vol 26 (34) ◽  
pp. 4234-4245
Author(s):  
Deepaneeta Sarmah ◽  
Aishika Datta ◽  
Swapnil Raut ◽  
Ankan Sarkar ◽  
Birva Shah ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Treatment Strategies ◽  
Cerebrovascular Diseases ◽  
Cellular Injury ◽  
Inflammatory Reactions ◽  
Inflammatory Pathways

Inflammation is a devastating outcome of cerebrovascular diseases (CVD), namely stroke and atherosclerosis. Numerous studies over the decade have shown that inflammasomes play a role in mediating inflammatory reactions post cellular injury occurring after a stroke or a rupture of an atherosclerotic plaque. In view of this, targeting these inflammatory pathways using different pharmacological therapies may improve outcomes in patients with CVD. Here, we review the mechanisms by which inflammasomes drive the pathogenesis of stroke and atherosclerosis. Also, discussed here are the possible treatment strategies available for inhibiting inflammasomes or their up-stream/down-stream mediators.

Transcutaneous Bilirubinometry: A New Light on an Old Subject

PEDIATRICS ◽  
1982 ◽  
Vol 69 (1) ◽  
pp. 124-125 ◽  
Author(s):  
Thomas Hegyi
Keyword(s):  
Central Nervous System ◽  
Skin Color ◽  
Serum Bilirubin ◽  
Cellular Injury ◽  
Bilirubin Concentration ◽  
Specific Serum ◽  
Relationship Of ◽  
The Relationship ◽  
Transcutaneous Bilirubinometry

The role of bilirubin as a cause of central nervous system morbidity in the newborn infant has been well recognized for several decades. The specific serum concentration that leads to cellular injury, as well as the precise mechanism of damage, are as yet unclear but general principles of therapy have been established. Early detection of hyperbilirubinemia is based on the clinical assessment of dermal icterus followed by appropriate serum tests to determine the degree of serum bilirubin elevation. The relationship of dermal icterus and serum bilirubin concentration has intrigued clinicians for more than a century.1 In an attempt to utilize skin color as an index of hyperbilirubinemia many techniques have been investigated.

Correlation between myocardial contractile force and cytosolic inorganic phosphate during early ischemia

1997 ◽  
Vol 272 (3) ◽  
pp. H1333-H1341 ◽  
Author(s):  
M. X. He ◽  
S. Wang ◽  
H. F. Downey
Keyword(s):  
Inorganic Phosphate ◽  
Contractile Force ◽  
Left Ventricular ◽  
Resonance Spectroscopy ◽  
Rat Hearts ◽  
Initial Control ◽  
Myocardial Contractile Force ◽  
Myocardial Contractile ◽  
Developed Pressure

To test the role of inorganic phosphate (Pi) in downregulation of myocardial contractile force at the onset of ischemia, Pi of rat hearts was determined with 31P nuclear magnetic resonance spectroscopy. Forty cycles of brief hypoperfusion (30% of baseline flow for 33 s) were used to achieve a time resolution of 0.512 s for comparing dynamic changes in Pi and contractile force. Initial control values of left ventricular developed pressure (LVP), heart rate, and oxygen consumption were 136 +/- 11 mmHg, 236 +/- 4 beats/min, and 95 +/- 3 microl O2 x min(-1) x g(-1); these values were unchanged at the end of the experiment. During the first 10 s of hypoperfusion, Pi increased at a rate (percentage of the total observed change) faster than the decrease in LVP; Pi and LVP then changed at the same rate during the remainder of the hypoperfusion. ADP did not change in advance of LVP. Intracellular pH did not change. The results indicate that Pi plays an important role in initiating the downregulation of myocardial contractile force at the onset of ischemia. Perfusion pressure also declined faster than LVP at the onset of ischemia, indicating potential importance of vascular collapse in contractile downregulation during early ischemia.

Evolution of the diverse biological roles of inositols

2007 ◽  
Vol 74 ◽  
pp. 223-246 ◽  
Author(s):  
Robert H. Michell
Keyword(s):  
Membrane Trafficking ◽  
Cell Signalling ◽  
Compatible Solutes ◽  
Mirror Image ◽  
Membrane Phospholipids ◽  
Functional Diversification ◽  
Redox Reagent ◽  
Ca2 Channels ◽  
Mycobacterium Spp

Several of the nine hexahydroxycylohexanes (inositols) have functions in Biology, with myo-inositol (Ins) in most of the starring roles; and Ins polyphosphates are amongst the most abundant organic phosphate constituents on Earth. Many Archaea make Ins and use it as a component of diphytanyl membrane phospholipids and the thermoprotective solute di-L-Ins-1,1′-phosphate. Few bacteria make Ins or use it, other than as a carbon source. Those that do include hyperthermophilic Thermotogales (which also employ di-l-Ins-1,1′-phosphate) and actinomycetes such as Mycobacterium spp. (which use mycothiol, an inositol-containing thiol, as an intracellular redox reagent and have characteristic phosphatidylinositol-linked surface oligosaccharides). Bacteria acquired their Ins3P synthases by lateral gene transfer from Archaea. Many eukaryotes, including stressed plants, insects, deep-sea animals and kidney tubule cells, adapt to environmental variation by making or accumulating diverse inositol derivatives as ‘compatible’ solutes. Eukaryotes use phosphatidylinositol derivatives for numerous roles in cell signalling and regulation and in protein anchoring at the cell surface. Remarkably, the diradylglycerol cores of archaeal and eukaryote/bacterial glycerophospholipids have mirror image configurations: sn-2,3 and sn-1,2 respectively. Multicellular animals and amoebozoans exhibit the greatest variety of functions for PtdIns derivatives, including the use of PtdIns(3,4,5)P3 as a signal. Evolutionarily, it seems likely that (i) early archaeons first made myo-inositol approx. 3500 Ma (million years) ago; (ii) archeons brought inositol derivatives into early eukaryotes (approx. 2000 Ma?); (iii) soon thereafter, eukaryotes established ubiquitous functions for phosphoinositides in membrane trafficking and Ins polyphosphate synthesis; and (iv) since approx. 1000 Ma, further waves of functional diversification in amoebozoans and metazoans have introduced Ins(1,4,5)P3 receptor Ca2+ channels and the messenger role of PtdIns(3,4,5)P3.

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