THE EFFECT OF γ‐AMINOBUTYRIC ACID ON BRAIN MITOCHONDRIAL ATP SYNTHESIS<sup>1</sup>

Lee, L W; Liao, CL; Yatsu, Frank M.

doi:10.1111/j.1471-4159.1974.tb04396.x

Cited by 7 publications

(3 citation statements)

References 18 publications

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“…Under these conditions, we find the cortical energy charge of the adenylate pool to normalize quickly after the circulatory restoration, 22 and isolated brain mitochondria show unimpaired synthesis of ATP. 23 These results indicate that energydependent processes, rather than energy-synthesizing machinery, are particularly vulnerable to ischemia. That membrane in integrity is such a vulnerable, energy-dependent process is possible, but our data do not support a firm conclusion.…”

Section: Discussionmentioning

confidence: 85%

Brain Phospholipid Metabolism During Ischemia

Yatsu

1975

Stroke

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Abstract:Brain Phospholipid Metabolism During Ischemia• Molecular mechanisms accounting for the vulnerability of brain to ischemic damage are incompletely understood. To assess the role of membrane integrity, phospholipid metabolism is investigated in subcellular organelles of brain following varying degrees of ischemia. Global brain ischemia is produced in rabbits by combining hypotension and hypoxia (4% oxygen). Restoration of blood pressure and oxygen after a three-minute isoelectric EEG results in full recovery, while a five-minute isoelectric EEG results in either a lack of recovery or neurological deficits. Quantitative analysis of seven phospholipids in subcellular organelles shows no consistent pattern of phospholipid changes following ischemia. Incorporation of radioactive phosphate, on the other hand, discloses moderate alterations following five-minute ischemia. These findings indicate that brain ischemia provokes phospholipid changes, but their role in impairing membrane integrity and in initiating irreversible ischemic brain damage is uncertain.

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Section: Discussionmentioning

confidence: 85%

Brain Phospholipid Metabolism During Ischemia

Yatsu

1975

Stroke

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“…49 This would most likely affect endothelial GABA productions, especially when we have observed that GABA produced by endothelial cells regulate metabolism via fatty acid oxidation processes.…”

Section: Discussionmentioning

confidence: 99%

“…49 Therefore, we evaluated whether GABA increased the synthesis of ATP in endothelial cells and potential mechanism(s) involved. We observed that in the presence of LAG, an inhibitor of GABA synthesis, the steady-state basal levels of intracellular ATP decreased, whereas the levels of ATP increased in the presence of Gc.…”

Section: Discussionmentioning

confidence: 99%

γ-Aminobutyric Acid Is Synthesized and Released by the Endothelium

Sen

Roy

Bandyopadhyay

et al. 2016

Circulation Research

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Rationale: Gamma aminobutyric acid (GABA), a neurotransmitter of the central nervous system, is found in the systemic circulation of humans at a concentration between 0.5 and 3 μmol/L. However, the potential source of circulating GABA and its significance on the vascular system remains unknown. We hypothesized that endothelial cells (ECs) may synthesize and release GABA to modulate some functions in the EC and after its release into the circulation.Objective: To assess whether GABA is synthesized and released by the EC and its potential functions. Methods and Results: Utilizing the human umbilical vein ECs and aortic ECs, we demonstrated for the first time that ECs synthesize and release GABA from [1-14 C]glutamate. Localization of GABA and the presence of the GABA-synthesizing enzyme, glutamic acid decarboxylase in EC were confirmed by immunostaining and immunoblot analysis, respectively. The presence of GABA was further confirmed by immunohistochemistry in the EC lining the human coronary vessel. EC-derived GABA regulated the key mechanisms of ATP synthesis, fatty acid, and pyruvate oxidation in EC. GABA protected EC by inhibiting the reactive oxygen species generation and prevented monocyte adhesion by attenuating vascular cell adhesion molecule -1 and monocyte chemoattractant protein-1 expressions. GABA had no relaxing effect on rat aortic rings. GABA exhibited a dose-dependent fall in blood pressure. However, the fall in BP was abolished after pretreatment with pentolinium. from Perkin Elmer, MA, catalog NEC290E050UC, NEC255050UC, and NEC559010UC. All other chemicals unless specified were obtained from Sigma. Conclusions: Cell CultureHuman umbilical vein endothelial cells (HUVECs) were freshly isolated from umbilical cords from different donors after normal delivery (with approval from the Institutional Review Board of University of California at Los Angeles, LA, CA). Primary cultures of HUVEC were prepared as described 14 and used at passages 1 or 2. Primary cultures of human aortic endothelial cells (HAEC) at passage 2 or 3 were a generous gift from Dr M. Navab in the Department of Medicine, University of California, Los Angeles, 90095-1732, USA. Both HAEC and HUVEC were cultured in endothelial cell basal medium-2 (Lonza), and the medium was supplemented with Endothelial Growth Medium-2 Bullet kit (CC3162; Lonza) as per the manufacturer's instructions as described previously. 15PC12 cells were a generous gift from Dr E. Schweitzer, Semel Institute of Neuroscience and Human Behavior, University of California, Los Angeles. PC12 cells were cultured in DMEM supplemented with 5% FCS and 5% Horse serum. Human skin fibroblast (HSF) cells were a gift from Dr H. Coller, Molecular Cell and Developmental Biology, University of California, Los Angeles. HSF and THP1 were cultured in DMEM supplemented with 10% FBS. All cells were cultured until 70% confluent before downstream manipulations. Cell culture treatments were done under sterile conditions, for 24 hours unless specified. Glutamic acid decarboxylase (GAD) doubl...

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