Oleic Acid Inhibits Gap Junction Permeability and Increases Glucose Uptake in Cultured Rat Astrocytes

Lavado, Eva; Sánchez‐Abarca, Luis Ignacio; Tabernero, Arantxa; Bolaños, Juan P.; Medina, José M.

doi:10.1046/j.1471-4159.1997.69020721.x

Cited by 52 publications

(52 citation statements)

References 39 publications

(44 reference statements)

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“…Furthermore, it has been shown that C18:1 cis addition determines a dosedependent inhibition of GAP junction permeability in cultured rat astrocytes. The authors suggested that C18:1 cis may play an important role in the transduction pathway leading to the inhibition of intracellular communication (41).…”

Section: Discussionmentioning

confidence: 99%

Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells

Natali

Siculella

Salvati

et al. 2007

Journal of Lipid Research

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Glial cells play a pivotal role in brain fatty acid metabolism and membrane biogenesis. However, the potential regulation of lipogenesis and cholesterologenesis by fatty acids in glial cells has been barely investigated. Here, we show that physiologically relevant concentrations of various saturated, monounsaturated, and polyunsaturated fatty acids significantly reduce [1-14 C]acetate incorporation into fatty acids and cholesterol in C6 cells. Oleic acid was the most effective at depressing lipogenesis and cholesterologenesis; a decreased label incorporation into cellular palmitic, stearic, and oleic acids was detected, suggesting that an enzymatic step(s) of de novo fatty acid biosynthesis was affected. To clarify this issue, the activities of acetylcoenzyme A carboxylase (ACC) and FAS were determined with an in situ digitonin-permeabilized cell assay after incubation of C6 cells with fatty acids. ACC activity was strongly reduced (?80%) by oleic acid, whereas no significant change in FAS activity was observed. Oleic acid also reduced the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR). The inhibition of ACC and HMGCR activities is corroborated by the decreases in ACC and HMGCR mRNA abundance and protein levels. The downregulation of ACC and HMGCR activities and expression by oleic acid could contribute to the reduced lipogenesis and cholesterologenesis.-Natali, F., L. Siculella, S. Salvati, and G. V. Gnoni. Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells. J. Lipid Res. 2007Res. . 48: 1966Res. -1975. After white adipose tissue, the brain is the organ with the highest lipid content of the body. The biosynthesis and deposition of lipids play an important role in maintaining brain structure and function, for example, during development-associated biogenesis of neural cell membranes. It is well established that alterations in lipid metabolism are the cause of or are associated with many neurological diseases (1-3).Astrocytes, the major class of glial cells in the mammalian brain, play an active role in brain metabolism. These cells surround intraparenchymal blood capillaries so that they represent the first cellular barrier for nutrients and other substances entering the brain system. A metabolic coupling between astrocytes and neurons to maintain energy metabolism homeostasis has been described (4, 5). Metabolic regulation in the brain has been investigated extensively, and those studies focused mostly on carbohydrate and amino acid metabolism (for review, see Ref. 6). During neuronal activity, glucose taken up by astrocytes is converted into lactate, which is then released into the extracellular space to be used by neurons (6). Regarding lipid metabolism, astroglial ketone body synthesis, showing characteristics strikingly similar to those of hepatic ketogenesis (7), may represent an important pathway for brain energy production and/or biosynthetic processes. The involvement of fatty acids in cell death pathways, particularly in the con...

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Section: Discussionmentioning

confidence: 99%

Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells

Natali

Siculella

Salvati

et al. 2007

Journal of Lipid Research

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“…We have previously shown that ET-1 increases the rate of glucose uptake in astrocytes and that this effect is mimicked by other gap junction uncouplers such as CBX, oleic acid, arachidonic acid, or 18-a-glycyrrhetinic acid (Lavado et al, 1997;Sanchez-Alvarez et al, 2004;Tabernero et al, 1996a;Tabernero et al, 2001). To investigate the participation of Cx43 in the effect of ET-1 on the rate of glucose uptake and on the molecular mechanism underlying this event, we tested the effect of ET-1 and CBX in Cx43-silenced astrocytes.…”

Section: Cx43 Is Involved In the Increase In Glucosementioning

confidence: 95%

Connexin43 is involved in the effect of endothelin‐1 on astrocyte proliferation and glucose uptake

Herrero-González

Valle-Casuso

Sánchez‐Alvarez

et al. 2008

Glia

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In previous studies, we showed that endothelin-1 increased astrocyte proliferation and glucose uptake. These effects were similar to those observed with other gap junction inhibitors, such as carbenoxolone (CBX). Because 24-h treatment with endothelin-1 or CBX downregulates the expression of connexin43, the main protein forming astrocytic gap junctions, which can also be involved in proliferation, in this study, we addressed the possible role of connexin43 in the effects of endothelin-1. To do so, connexin43 was silenced in astrocytes by siRNA. The knock down of connexin43 increased the rate of glucose uptake, characterized by the upregulation of GLUT-1 and type I hexokinase. Neither endothelin-1 nor CBX were able to further increase the rate of glucose uptake in connexin43-silenced astrocytes. In agreement, no effects of endothelin-1 and CBX on GLUT-1 and type I hexokinase were observed in connexin-43 silenced astrocytes or in astrocytes from connexin43 knock-out (KO) mice. Our previous studies suggested a close relationship between glucose uptake and astrocyte proliferation. Consistent with this, connexin43-silenced astrocytes exhibited an increase in Ki-67, a marker of proliferation. The effects of ET-1 on retinoblastoma phosphorylation on Ser780 and on the upregulation of cyclins D1 and D3 were affected by the levels of connexin43. In conclusion, our results indicate that connexin43 participates in the effects of endothelin-1 on glucose uptake and proliferation in astrocytes. Interestingly, although the rate of growth in connexin43 KO astrocytes has been reported to be reduced, we observed that an acute reduction in connexin43 by siRNA increased proliferation and glucose uptake. V V C

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“…To examine whether the signal mediating the intercellular calcium waves propagated from cell to cell through gap junctions, experiments were performed on strips incubated during 20 min with physiological solution supplemented with PA, a gap junctions uncoupler (13). Strips showing calcium waves under local PE stimulations in the presence of 0.3 M PE in the superfusion did not show any propagation after treatment with PA (50 M), although 0.3 M PE was still present in the superfusion (Fig.…”

Section: Characterization Of the Vasomotion Propagation: Calcium And mentioning

confidence: 99%

Intercellular calcium waves are associated with the propagation of vasomotion along arterial strips

Seppey

Sauser

Koenigsberger

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Oleic Acid Inhibits Gap Junction Permeability and Increases Glucose Uptake in Cultured Rat Astrocytes

Cited by 52 publications

References 39 publications

Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells

Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells

Connexin43 is involved in the effect of endothelin‐1 on astrocyte proliferation and glucose uptake

Intercellular calcium waves are associated with the propagation of vasomotion along arterial strips

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