Oleic acid increases mitochondrial reactive oxygen species production and decreases endothelial nitric oxide synthase activity in cultured endothelial cells

Gremmels, Hendrik; Bevers, Lonneke M.; Fledderus, Joost O.; Braam, Branko; Zonneveld, Anton Jan van; Verhaar, Marianne C.; Joles, Jaap A.

doi:10.1016/j.ejphar.2015.01.005

Cited by 40 publications

(39 citation statements)

References 31 publications

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“…Some authors observed that OA reduced the expression of VCAM‐1 and ICAM‐1 on human umbilical vein ECs (HUVECs), as well as the levels of the pro‐inflammatory cytokines TNF‐α, IL‐6, and MCP‐1, protecting the cells from the pro‐apoptotic and inflammatory effects of PA and stearate . However, higher levels of OA (400 μM) were found to lead to production of mitochondrial‐derived reactive oxygen species and hence endothelial dysfunction …”

Section: Introductionmentioning

confidence: 99%

Palmitoleic Acid has Stronger Anti‐Inflammatory Potential in Human Endothelial Cells Compared to Oleic and Palmitic Acids

Souza

Valenzuela

Baker

et al. 2018

Molecular Nutrition Food Res

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Section: Introductionmentioning

confidence: 99%

Palmitoleic Acid has Stronger Anti‐Inflammatory Potential in Human Endothelial Cells Compared to Oleic and Palmitic Acids

Souza

Valenzuela

Baker

et al. 2018

Molecular Nutrition Food Res

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“…As GT1-7 cells respond to oleate by activation of K ATP and cell hyperpolarization such a mechanism was unlikely to also explain this outcome. Alternatively, increased fatty acid oxidation could raise reactive oxygen species levels (Ruiz-Ramírez et al, 2011, Arany et al, 2013, Gremmels et al, 2015) previously implicated in pathways leading to neuronal K ATP activation (Chai and Lin, 2010). Thus in order to examine the role of fatty acid metabolism via β-oxidation we prevented the delivery of oleate to mitochondria by inhibition of carnitine palmitoyltransferase-1 (CPT1).…”

Section: Resultsmentioning

confidence: 99%

“…An alternative mechanism by which mitochondrial oxidation of oleate could increase K ATP activity and cause cell hyperpolarization is via the enhanced production of reactive oxygen species (Larsson et al, 1996, Arany et al, 2013, Gremmels et al, 2015). Importantly, the effects of oleate on energy and glucose homeostasis have been shown to be dependent on hypothalamic CPT1 activity (Obici et al, 2003, Pocai et al, 2006), indicative of fatty acid oxidation regulating hypothalamic neurons.…”

Section: Discussionmentioning

confidence: 99%

Oleate induces K ATP channel-dependent hyperpolarization in mouse hypothalamic glucose-excited neurons without altering cellular energy charge

et al. 2017

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HighlightsOleate and low glucose hyperpolarize and inhibit GT1-7 and mouse GE neurons by activation of KATP.Oleate inhibition of GT1-7 neuron activity is not mediated by AMPK or fatty acid oxidation.Activation of KATP by oleate requires ATP hydrolysis but does not reduce the levels ATP or the ATP:ADP ratio.GT1-7 hyperpolarization by oleate is not dependent on UCP2.Oleate and low glucose depolarize a subpopulation of hypothalamic GI neurons.

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“…The effect of Nrf2 pathway modulation on intracellular ROS was determined using 5,6-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate, (CM-H 2 DCFDA, Life Technologies) [34]. ECFCs were incubated for 1 hour with 5 μ g/ml CM-H 2 DCFDA, washed once, and were allowed to recover for 30 minutes before being exposed to increasing concentration of H 2 O 2 .…”

Section: Methodsmentioning

confidence: 99%

The Transcription Factor Nrf2 Protects Angiogenic Capacity of Endothelial Colony-Forming Cells in High-Oxygen Radical Stress Conditions

Gremmels

Jong

Hazenbrink

et al. 2017

Stem Cells International

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Background Endothelial colony forming cells (ECFCs) have shown a promise in tissue engineering of vascular constructs, where they act as endothelial progenitor cells. After implantation, ECFCs are likely to be subjected to elevated reactive oxygen species (ROS). The transcription factor Nrf2 regulates the expression of antioxidant enzymes in response to ROS. Methods Stable knockdown of Nrf2 and Keap1 was achieved by transduction with lentiviral shRNAs; activation of Nrf2 was induced by incubation with sulforaphane (SFN). Expression of Nrf2 target genes was assessed by qPCR, oxidative stress was assessed using CM-DCFDA, and angiogenesis was quantified by scratch-wound and tubule-formation assays Results. Nrf2 knockdown led to a reduction of antioxidant gene expression and increased ROS. Angiogenesis was disturbed after Nrf2 knockdown even in the absence of ROS. Conversely, angiogenesis was preserved in high ROS conditions after knockdown of Keap1. Preincubation of ECFCs with SFN reduced intracellular ROS in the presence of H2O2 and preserved scratch-wound closure and tubule-formation. Results Nrf2 knockdown led to a reduction of antioxidant gene expression and increased ROS. Angiogenesis was disturbed after Nrf2 knockdown even in the absence of ROS. Conversely, angiogenesis was preserved in high ROS conditions after knockdown of Keap1. Preincubation of ECFCs with SFN reduced intracellular ROS in the presence of H2O2 and preserved scratch-wound closure and tubule-formation. Conclusion The results of this study indicate that Nrf2 plays an important role in the angiogenic capacity of ECFCs, particularly under conditions of increased oxidative stress. Pretreatment of ECFCs with SFN prior to implantation may be a protective strategy for tissue-engineered constructs or cell therapies.

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Oleic acid increases mitochondrial reactive oxygen species production and decreases endothelial nitric oxide synthase activity in cultured endothelial cells

Cited by 40 publications

References 31 publications

Palmitoleic Acid has Stronger Anti‐Inflammatory Potential in Human Endothelial Cells Compared to Oleic and Palmitic Acids

Palmitoleic Acid has Stronger Anti‐Inflammatory Potential in Human Endothelial Cells Compared to Oleic and Palmitic Acids

Oleate induces K ATP channel-dependent hyperpolarization in mouse hypothalamic glucose-excited neurons without altering cellular energy charge

The Transcription Factor Nrf2 Protects Angiogenic Capacity of Endothelial Colony-Forming Cells in High-Oxygen Radical Stress Conditions

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