The differentiation of phospholipase a1 and a2 in rat and human nervous tissues
TL;DR: Lipid‐free extracts of rat and human brain have been prepared and shown to contain phospholipase A1 and A2 activities and a lysophospholip enzyme, which hydrolyse the ester bond at the 1‐position in lecithin, phosphatidyl‐ethanolamine and phosphatin, but have little or no action on triglyceride or cholesterol ester.
Abstract: —Lipid-free extracts of rat and human brain have been prepared and shown to contain phospholipase A1 and A2 activities and a lysophospholipase. The phospholipase Aj activity has pH optima of 4·2 and 4·6 in rat and human brain, respectively; it can be partially purified and isolated in high yields by dialysing the extracts at low pH. The purified preparations hydrolyse the ester bond at the 1-position in lecithin, phosphatidyl-ethanolamine and phosphatidylserine, but have little or no action on triglyceride or cholesterol ester. An assay system for the enzyme is described.
Phospholipase A2 activity is optimal at pH 5·5 in rat brain extracts and at pH 5·0 in extracts of human brain. The phospholipase A2 activity of human cerebral cortex is largely unaffected by heating extracts at 70°C for 5 min, whereas this treatment substantially inactivates phospholipase A1 and completely destroys lysophospholipase.
Phospholipase A1 is widely distributed in both grey and white matter of human brain and is also present in peripheral nerve. Phospholipase A2 activity is lower than A1 in all regions of the CNS examined so far, and is absent from peripheral nerve. Neither enzyme appears to require Ca2+ but both are inhibited by di-isopropylfluorophosphate (DFP, 2 × 10−6 m) and thus differ from phospholipase A of pancreas.
These studies confirm that the phospholipase A1 and A2 activities in brain are due to separate enzymes.
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TL;DR: In this article, it was shown that the clinically most important conditions leading to brain cell death are those associated with cerebrovascul ar dise ase, particularly stroke, and with head trauma.
Abstract: All cells in living organisms have a limited life span, and when the time set by their biological clocks has run out, they will die , their highly orga nized macromolec ular structure will disintegrate, and the low-molec ul ar degrad ation products be come part of the disorder of the surroundings . In thermodynamic terms, this series of events consti tutes what has been c alled the entropic doom. We know little about those molec ul ar mechanisms that limit the life span of cells in the absence of dise ase. For the clinician, therefore, the important task is to prevent or tre at dise ases that jeopardize the proper functioning and viability of cells whose biologic al clocks have not yet run out . Measures instituted to prevent brain cell death have a special importance . This i s partly due t o the fact that w e equate human life with the functioning of the brain. However, this importance also resides in the v ulnerability of brain cells to conditions that allow cells of most other tissue to survive , and to continue or res ume their activitie s . The clinically most important conditions leading to brain cell death are those associated with cere brovascul ar dise ase, particularly stroke, and with head trauma. We will begin, though, by rec alling the traditional view of the occ urrence and loc alization of neuronal damage in four conditions that lead to more disseminated alterations, e specially since they have been considered to c ause nerve cell injury of a
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TL;DR: Platelets in the blood of volunteers who have taken aspirin can no longer produce prostaglandins, and these platelets are removed from the body by the immune system.
Abstract: Platelets in the blood of volunteers who have taken aspirin can no longer produce prostaglandins.
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TL;DR: The period of discovery of new lipids in the nervous system appears to be over and all the major lipid components have been discovered and a great deal is now known about their structure and metabolism.
694 citations
TL;DR: The traditional view of the occ urrence and loc alization of neuronal damage in four conditions that lead to more disseminated alterations is resumed, e specially since they have been considered to c ause nerve cell injury of a stroke and with head trauma.
Abstract: All cells in living organisms have a limited life span, and when the time set by their biological clocks has run out, they will die , their highly orga nized macromolec ular structure will disintegrate, and the low-molec ul ar degrad ation products be come part of the disorder of the surroundings . In thermodynamic terms, this series of events consti tutes what has been c alled the entropic doom. We know little about those molec ul ar mechanisms that limit the life span of cells in the absence of dise ase. For the clinician, therefore, the important task is to prevent or tre at dise ases that jeopardize the proper functioning and viability of cells whose biologic al clocks have not yet run out . Measures instituted to prevent brain cell death have a special importance . This i s partly due t o the fact that w e equate human life with the functioning of the brain. However, this importance also resides in the v ulnerability of brain cells to conditions that allow cells of most other tissue to survive , and to continue or res ume their activitie s . The clinically most important conditions leading to brain cell death are those associated with cere brovascul ar dise ase, particularly stroke, and with head trauma. We will begin, though, by rec alling the traditional view of the occ urrence and loc alization of neuronal damage in four conditions that lead to more disseminated alterations, e specially since they have been considered to c ause nerve cell injury of a
337 citations
TL;DR: The action of phospholipase A and lysophosphatidyl choline on mature, myelinated peripheral nerve fibres has been studied in vivo and electron microscopically, following sub-perineurial injection of these substances, and its potential involvement in pathological demyelination is discussed.
Abstract: The action of phospholipase A and lysophosphatidyl choline (LPC) on mature, myelinated peripheral nerve fibres has been studied in vivo and electron microscopically, following sub-perineurial injection of these substances. Within 30 min, demyelination was observed in vivo along cylindrico-conical segments, spreading from Schmidt-Lanterman incisures and nodes of Ranvier. By 96 h, all traces of the myelin sheath had disappeared from the area of the lesion, and had been replaced by debris-laden cells lying in chains parallel to one another and the long axis of the fibre. During the next few weeks these cells gradually disappeared, and numerous finely myelinated axons, running between, and in continuity with, the normal fibres proximal and distal to the lesion were observed. If lower concentrations of LPC were used the number of fibres involved decreased, although the demyelinative changes followed the same time-course. Ultrastructurally, demyelination involved progressive disruption and removal of the lamellar sheath, observed initially as a splitting of the intraperiod line within 30 min. Subsequent breakdown resulted in the formation of strands of 4-6 nm repeat material which was further degraded through quintuple- and triple-layered lamellar units to foam-like systems of disorganized lamellar fragments. The Schwann cell and axons appeared to be undamaged by phospholipase A and LPC, and retained their normal impermeability to exogenous ferritin. The significance of the demyelinating capacity of LPC in vivo is discussed in terms of its known action on myelin in vitro , the rapidity and apparent specificity of its action demonstrated in this study, and its potential involvement in pathological demyelination.
197 citations
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