Effect of Hypoxic-Ischemic Injury on Serine Palmitoyltransferase Activity in the Developing Rat Brain

J. Neurochem. (2010) 115, 168–177. Abstract Acute administration of ethanol to 7‐day‐old mice is known to cause robust apoptotic neurodegeneration in the brain. Our previous studies have shown that such ethanol‐induced neurodegeneration is accompanied by increases in lipids, including ceramide, triglyceride (TG), cholesterol ester (ChE), and N‐acylphosphatidylethanolamine (NAPE) in the brain. In this study, the effects of ethanol on lipid profiles as well as caspase 3 activation were examined in the cortex, hippocampus, cerebellum, and inferior colliculus of the postnatal day 7 mouse brain. We found that the cortex, hippocampus, and inferior colliculus, which showed substantial caspase 3 activation by ethanol, manifested significant elevations in ceramide, TG, and NAPE. In contrast, the cerebellum, with the least caspase 3 activation, failed to show significant changes in ceramide and TG, and exhibits much smaller increases in NAPE than other brain regions. Ethanol‐induced increases in ChE were observed in all brain regions tested. Inhibitors of serine palmitoyltransferase effectively blocked ethanol‐induced caspase 3 activation as well as elevations in ceramide, ChE, and NAPE. Immunohistochemical studies indicated that the expression of serine palmitoyltransferase was mainly localized in neurons and was enhanced in activated caspase 3‐positive neurons generated by ethanol. These results indicate that de novo ceramide synthesis has a vital role in ethanol‐induced apoptotic neurodegeneration in the developing brain.

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“…Serine palmitoyltransferase activity was measured according to the methods of Rutti et al. (2009) and Daigo et al. (2008).…”

Section: Methodsmentioning

confidence: 99%

“…Serine palmitoyltransferase activity was measured according to the methods of Rutti et al (2009) and Daigo et al (2008). In brief, forebrain samples were homogenized in 0.32 M sucrose containing 2.5 mM EDTA, 1 mM dithiothreitol, and 50 mM HEPES buffer (pH 8.0), and the microsomal fractions were prepared.…”

Section: Serine Palmitoyltransferase Assaymentioning

confidence: 99%

Involvement of ceramide in ethanol‐induced apoptotic neurodegeneration in the neonatal mouse brain

Saito

Chakraborty

Hegde

et al. 2010

Journal of Neurochemistry

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“…A series of mutant animals lacking PLP (Boison et al, 1995; Rosenbluth et al, 1996; Klugmann et al, 1997) as well as several human disorders involving the PLP gene (Griffiths et al, 1998; Daigo et al, 2008; Tanaka et al, 2009) display severe neurological impairment, emphasizing the physiological importance of this protein in nervous system. In the absence of myelin sheath, as seen in demyelization diseases, impulse conduction is impeded resulting in severe sensory and motor deficits (Boison & Stoffel, 1994).…”

Section: Discussionmentioning

confidence: 99%

Ethanol down regulates the expression of myelin proteolipid protein in the rat hippocampus

et al. 2010

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It is well known that chronic ethanol treatment affects the synthesis of RNA and protein in the brain and the maintenance and function of nervous system. The changes in myelination-related genes are most prominent in human alcoholics. Previously, our cDNA microarray study showed altered Proteolipid protein (PLP), a major protein of central myelin. The present study aimed to gain more understanding of the expression of PLP after chronic ethanol treatment. Male Sprague-Dawley rats were daily treated with ethanol (15% in saline, 3 g/kg, i.p.) or saline for 14 days. Messenger RNAs from hippocampus of each group were subjected to cDNA expression array hybridization to determine the differential gene expressions. Among many ethanol responsive genes, PLP was negatively regulated by ethanol treatment, which is one of the most abundant proteins in the CNS and has an important role in the stabilization of myelin sheath. Using northern blot and immunohistochemical analysis, we showed the change in expression level of PLP mRNA and protein after ethanol treatment. PLP mRNA and protein were decreased in hippocampus of rat with chronic ethanol exposure, suggesting that ethanol may affect the stabilization of myelin sheath through the modulation of PLP expression and induce the pathophysiology of alcoholic brain.

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“…While MerTK are the main domain in TAM receptor kinases that activate anti-inflammatory growth (which mediated by Ang2-AT2 productions) to protect from Rheumatoid Arthritis [74].…”

Section: The Role Of Tam Receptors Includes Axl Receptor (Which Is Ty...mentioning

confidence: 99%

Pyrimidine TAT TAC Kinases Promote B-Arrestins and Rac1 for Adopting Myocardial Constrictions and Gpcrs Ratio by Ang2-AT2 Synthesis and Anti-Inflammatory Growth

Tantawi¹

2022

Jap J Clin & Med Res

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The orphan nuclear pathway (regulated by pyrimidine TAT and TAC kinases and OPA1 enzymes) has the roles of producing the Beta-subunit (fatty Acyl-COAbeta) upon the effects of synthase which regulate B-arrestins synthesis for adopting ACE for Ang2-AT2 synthesis from Ang1-AT1 (that adopt GPCRs ratio) . The inhibition in synthase and in pyrimidines kinases will reflect Inhibition in Acyl-COA-beta synthesis followed by cholesterol and long fatty chains accumulations with high affinity to bind with k and Na salts that can precipitated and cause lipotoxicity. B-arrestins play a well established role in the dampening of G-protein coupled receptors (GPCRs) accumulation, that prevent their increasing through its adopting to ACE for activating Ang2-AT2 synthesis from Ang1-AT1.

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Effect of Hypoxic-Ischemic Injury on Serine Palmitoyltransferase Activity in the Developing Rat Brain

Cited by 6 publications

References 47 publications

Involvement of ceramide in ethanol‐induced apoptotic neurodegeneration in the neonatal mouse brain

Involvement of ceramide in ethanol‐induced apoptotic neurodegeneration in the neonatal mouse brain

Ethanol down regulates the expression of myelin proteolipid protein in the rat hippocampus

Pyrimidine TAT TAC Kinases Promote B-Arrestins and Rac1 for Adopting Myocardial Constrictions and Gpcrs Ratio by Ang2-AT2 Synthesis and Anti-Inflammatory Growth

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