Abstract
To evaluate possible involvement of phospholipid metabolism and related second messenger systems in the selective neuronal damage after ischemia, we measured changes of polyphosphoinositides (PPIs) and free fatty acids (FFAs) in a model of 5-min or 10-min ischemia and reperfusion in gerbils. The binding activity of 3H-phorbol 12, 13-dibutyrate (PDBu) for protein kinase C (PKC) and 3H-inositol 1,4,5-triphosphate (IP3) for IP3 receptors was demonstrated autoradiographically. Induction of 70 KDa heat shock protein (HSP70) mRNA and amyloid precursor protein (APP) mRNA was also examined using Northern blot analysis.
In the parietal cortex (an area resistant to transient ischemia), PPIs decreased during ischemia and recovered rapidly after reperfusion. However, recovery did not occur in the hippocampal CA1 area (an area more vulnerable to transient ischemia). In the cortex, arachidonic acid (AA) increased during ischemia and returned to baseline by 7 days after reperfusion; in the CA1 area, the AA level remained elevated even after 7 days of reperfusion.
PDBu binding decreased in CA1 cells after 2 days of reperfusion. IP3 binding began to decrease at 5 hr of reperfusion, which is far earlier than either the onset of decreased PDBu binding or the observation of neuronal damage by light microscopy.
The induction of HSP70 mRNA occurred, but the induction of APP mRNA did not. Regional differences in the induction of HSP70 mRNA were found; CA1 cells produced less HSP70 mRNA than cortical cells 8 hr after transient ischemia.
These results suggest that CA1 cell membranes may not recover after transient ischemic attack, and that the membranes of the endoplasmic reticulum, which have IP3 receptors, may undergo alterations earlier than cytoplasmic membranes. The variable induction of HSP70 mRNA may be related to regional differences in vulnerability in cortical and hippocampal CA1 cells after transient ischemia. Involvement of excitatory neurotransmission in the induction of HSP70 has been suggested. The combined data may support a role for inositol phospholipid metabolism, changes in related second messenger systems, and induction of HSP70 in the excitotoxic mechanism of hippocampal CA1 neuronal damage, death, and repair.
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References
Abe K and Kogure K (1986) Accurate evaluation of 1,2-diacylglycerol in gerbil forebrain using HPLC and in situfreezing technique. J Neurochem 47: 577–582.
Abe K, Kawagoe J, Sato S, Kogure K (1991a) Induction of zinc-finger gene after transient focal ischemia in rat cerebral cortex. Neurosci Lett 123: 248–250.
Abe K, Kogure K, Yamamoto H, Imazawa M, Miyamoto K (1987) Mechanisms of arachidonic acid liberation during ischemia in gerbil cerebral cortex. J Neurochem 48: 503–509.
Abe K, Tanzi RE, Kogure K (1991b) Induction of HSP70 mRNA after transient ischemia in gerbil brain. Neurosci Lett 125: 166–168.
Aizenman E, Hartnett KA, Reynolds IJ (1990) Oxygen free radicals regulated NMDA receptor function via a redox modulatory site. Neuron 5: 841–846.
Bazan NG (in press) Significance of phospholipase A2 activation and second messengers in brain damage. Prog Brain Res.
Benveniste H, Drejer J, Schousboe A, Diemer NH (1984) Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J Neurochem 43: 1369–1374.
Dumuis A, Sebben M, Haynes L, Pin J-P, Bockert J (1988) NMDA receptors activate the arachidonic acid cascade system in striatal neurons. Nature 336: 68–70.
Irvine RF, Letcher AJ, Heslop JP, Berridge MJ (1986) The inositol tris/tetrakisphosphate pathway demonstration of Ins(l,4,5)P3 3-kinase activity in animal tissues. Nature 320: 631–634.
Kirino T (1982) Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res 239: 57–69.
Lowe DG and Moran LA (1986) Molecular cloning and analysis of DNA complementary to three mouse Mr=68000 heat shock protein mRNA. J Biol Chem 261: 2102–2112.
Magnussen KG and Wieloch TW (1989) Impairment of protein ubiquitination may cause delayed neuronal death. Neurosci Lett 96: 264–270.
Marini AM, Kozuka M, Lipsky RH, Nowak TS Jr. (1990) 70-kilodalton heat shock protein induction in cerebellar astrocytes and cerebellar granule cells in vitroComparison with immunocytochemical location after hyperthermia in vivo.. J Neurochem 54: 1509–1516.
Nicoletti F, Meek, JL, Iadarola Mj, Chuang DM, Roth BL, Costa E (1986) Coupling of inositol phospholipid metabolism with excitatory amino acid recognition sites in rat hippocampus. J Neurochem 46: 40–46.
Nowak TS Jr (1991) Localization of 70 KDa stress protein mRNA induction in gerbil brain after ischemia. J Cereb Blood Flow Metab 11: 432–439.
Ordway RW, Singer JJ, Walsh JV Jr (1991) Direct regulation of ion channels by fatty acids. Trends Neurosci 14: 96–100.
Rothman SM and Olney JW (1986) Glutamate and pathophysiology of hypoxicischemic brain damage. Ann Neurol 19: 105–111.
Salbaum JM, Weidermann A, Lemaire HG, Masters CL, Beyreuter K (1988) The promoter of Alzheimer’s disease amyloid A4 precursor gene. EMBO J 7: 2807–2819.
Vass K, Welch WJ, Nowak TS Jr (1988) Localization of 70kDa stress protein induction in gerbil brain after ischemia. Acta Neuropathol 77: 128–135.
Westerberg E and Wieloch T (1986) Lesions to the corticostriatal pathways ameliorate hypoglycemia-induced arachidonic acid release. J Neurochem 47: 1507–1511.
Wieloch T (1985) Neurochemical correlates to selective neuronal vulnerability. Prog Brain Res 63: 69–85.
Worley PF, Baraban JM, Snyder SH (1987) Beyond receptors: Multiple second-messenger systems in brain. Ann Neurol 217–229.
Wu B, Hunt C, Morimoto R (1985) Structure and expression of the human gene encoding major heat shock protein HSP70. Mol Cell Biol 5: 330–341.
Yoshimi K, Kudo T, Iwata N, Nishimura K (1990) Change of clathrin precedes delayed neuronal death of CA1 cells after ischemia. Jpn J Neurochem 29: 456–457.
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Abe, K., Araki, T., Kawagoe, Ji., Aoki, M., Kogure, K. (1992). Phospholipid Metabolism and Second Messenger System After Brain Ischemia. In: Bazan, N.G., Murphy, M.G., Toffano, G. (eds) Neurobiology of Essential Fatty Acids. Advances in Experimental Medicine and Biology, vol 318. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3426-6_16
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DOI: https://doi.org/10.1007/978-1-4615-3426-6_16
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