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Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production.

Lin MC, Lin CF, Li CF, Sun DP, Wang LY, Hsing CH - Int J Mol Sci (2015)

Bottom Line: In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs.In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1).Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Chi Mei Medical Center, Liouying, 201, Taikang, Taikang Village, Liuying District, Tainan 736, Taiwan. mygegon@gmail.com.

ABSTRACT
Prolonged treatment with a large dose of propofol may cause diffuse cellular cytotoxicity; however, the detailed underlying mechanism remains unclear, particularly in vascular endothelial cells. Previous studies showed that a propofol overdose induces endothelial injury and vascular barrier dysfunction. Regarding the important role of endothelial glycocalyx on the maintenance of vascular barrier integrity, we therefore hypothesized that a propofol overdose-induced endothelial barrier dysfunction is caused by impaired endothelial glycocalyx. In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs. In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1). Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells. These results demonstrate that a propofol overdose induces a partially ATP-dependent reduction of endothelial glycocalyx expression and consequently leads to vascular hyperpermeability due to the loss of endothelial barrier functions.

No MeSH data available.


Related in: MedlinePlus

Propofol overdose effect on ATP production and endothelial glycocalyx in HMEC-1 cells. HMEC-1 cells were treated with nothing, propofol or oligomycin for 16 h. NAD+/NADH assay was used to detect the (A) NAD+/NADH ratio and an ATP assay to detect (B) ATP production in HMEC-1 cells; (C) HMEC-1 cells were treated with PBS, propofol or oligomycin for 16 h. The relative expression levels of SDC-1, SDC4, PLC and GPC-1 mRNA in HMEC-1 cells were detected using RT-PCR. The ratios and ratios to the untreated control are shown as means ± SD of triplicate cultures. * p < 0.05, ** p < 0.01, *** p < 0.001 compared with the untreated group.
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ijms-16-12092-f005: Propofol overdose effect on ATP production and endothelial glycocalyx in HMEC-1 cells. HMEC-1 cells were treated with nothing, propofol or oligomycin for 16 h. NAD+/NADH assay was used to detect the (A) NAD+/NADH ratio and an ATP assay to detect (B) ATP production in HMEC-1 cells; (C) HMEC-1 cells were treated with PBS, propofol or oligomycin for 16 h. The relative expression levels of SDC-1, SDC4, PLC and GPC-1 mRNA in HMEC-1 cells were detected using RT-PCR. The ratios and ratios to the untreated control are shown as means ± SD of triplicate cultures. * p < 0.05, ** p < 0.01, *** p < 0.001 compared with the untreated group.

Mentions: Because propofol potentially interferes with cellular energy utilization [3] and because of our previous findings of propofol-induced mitochondrial apoptosis [38], we tested the effect of cellular ATP production on endothelial glycocalyx by treating HMEC-1 cells with oligomycin, an ATP synthase inhibitor. The NAD+/NADH assay showed that the NAD+/NADH ratio was significantly (p < 0.001) lower in propofol-overdosed cells (Figure 5A), and the ATP assay showed that the ATP concentration was significantly (p < 0.05 and p < 0.01) lower in both the propofol-overdosed and oligomycin-treated cells (Figure 5B). Moreover, RT-PCR showed that the relative expression of syndecan-4, perlecan and glypican-1 mRNA was significantly (p < 0.05) lower in cells overdosed with propofol or treated with oligomycin for 16 h (Figure 5C).


Anesthetic propofol overdose causes vascular hyperpermeability by reducing endothelial glycocalyx and ATP production.

Lin MC, Lin CF, Li CF, Sun DP, Wang LY, Hsing CH - Int J Mol Sci (2015)

Propofol overdose effect on ATP production and endothelial glycocalyx in HMEC-1 cells. HMEC-1 cells were treated with nothing, propofol or oligomycin for 16 h. NAD+/NADH assay was used to detect the (A) NAD+/NADH ratio and an ATP assay to detect (B) ATP production in HMEC-1 cells; (C) HMEC-1 cells were treated with PBS, propofol or oligomycin for 16 h. The relative expression levels of SDC-1, SDC4, PLC and GPC-1 mRNA in HMEC-1 cells were detected using RT-PCR. The ratios and ratios to the untreated control are shown as means ± SD of triplicate cultures. * p < 0.05, ** p < 0.01, *** p < 0.001 compared with the untreated group.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4490431&req=5

ijms-16-12092-f005: Propofol overdose effect on ATP production and endothelial glycocalyx in HMEC-1 cells. HMEC-1 cells were treated with nothing, propofol or oligomycin for 16 h. NAD+/NADH assay was used to detect the (A) NAD+/NADH ratio and an ATP assay to detect (B) ATP production in HMEC-1 cells; (C) HMEC-1 cells were treated with PBS, propofol or oligomycin for 16 h. The relative expression levels of SDC-1, SDC4, PLC and GPC-1 mRNA in HMEC-1 cells were detected using RT-PCR. The ratios and ratios to the untreated control are shown as means ± SD of triplicate cultures. * p < 0.05, ** p < 0.01, *** p < 0.001 compared with the untreated group.
Mentions: Because propofol potentially interferes with cellular energy utilization [3] and because of our previous findings of propofol-induced mitochondrial apoptosis [38], we tested the effect of cellular ATP production on endothelial glycocalyx by treating HMEC-1 cells with oligomycin, an ATP synthase inhibitor. The NAD+/NADH assay showed that the NAD+/NADH ratio was significantly (p < 0.001) lower in propofol-overdosed cells (Figure 5A), and the ATP assay showed that the ATP concentration was significantly (p < 0.05 and p < 0.01) lower in both the propofol-overdosed and oligomycin-treated cells (Figure 5B). Moreover, RT-PCR showed that the relative expression of syndecan-4, perlecan and glypican-1 mRNA was significantly (p < 0.05) lower in cells overdosed with propofol or treated with oligomycin for 16 h (Figure 5C).

Bottom Line: In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs.In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1).Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology, Chi Mei Medical Center, Liouying, 201, Taikang, Taikang Village, Liuying District, Tainan 736, Taiwan. mygegon@gmail.com.

ABSTRACT
Prolonged treatment with a large dose of propofol may cause diffuse cellular cytotoxicity; however, the detailed underlying mechanism remains unclear, particularly in vascular endothelial cells. Previous studies showed that a propofol overdose induces endothelial injury and vascular barrier dysfunction. Regarding the important role of endothelial glycocalyx on the maintenance of vascular barrier integrity, we therefore hypothesized that a propofol overdose-induced endothelial barrier dysfunction is caused by impaired endothelial glycocalyx. In vivo, we intraperitoneally injected ICR mice with overdosed propofol, and the results showed that a propofol overdose significantly induced systemic vascular hyperpermeability and reduced the expression of endothelial glycocalyx, syndecan-1, syndecan-4, perlecan mRNA and heparan sulfate (HS) in the vessels of multiple organs. In vitro, a propofol overdose reduced the expression of syndecan-1, syndecan-4, perlecan, glypican-1 mRNA and HS and induced significant decreases in the nicotinamide adenine dinucleotide (NAD+)/NADH ratio and ATP concentrations in human microvascular endothelial cells (HMEC-1). Oligomycin treatment also induced significant decreases in the NAD+/NADH ratio, in ATP concentrations and in syndecan-4, perlecan and glypican-1 mRNA expression in HMEC-1 cells. These results demonstrate that a propofol overdose induces a partially ATP-dependent reduction of endothelial glycocalyx expression and consequently leads to vascular hyperpermeability due to the loss of endothelial barrier functions.

No MeSH data available.


Related in: MedlinePlus