Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study
Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a multisystem chronic illness characterized by severe muscle fatigue, pain, dizziness, and brain fog. Many patients with ME/CFS experience orthostatic intolerance (OI), which is characterized by frequent dizziness, light-headedness, a...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/10/8713 |
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| author | Carl Gunnar Gottschalk Ryan Whelan Daniel Peterson Avik Roy |
| author_facet | Carl Gunnar Gottschalk Ryan Whelan Daniel Peterson Avik Roy |
| author_sort | Carl Gunnar Gottschalk |
| collection | DOAJ |
| description | Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a multisystem chronic illness characterized by severe muscle fatigue, pain, dizziness, and brain fog. Many patients with ME/CFS experience orthostatic intolerance (OI), which is characterized by frequent dizziness, light-headedness, and feeling faint while maintaining an upright posture. Despite intense investigation, the molecular mechanism of this debilitating condition is still unknown. OI is often manifested by cardiovascular alterations, such as reduced cerebral blood flow, reduced blood pressure, and diminished heart rate. The bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of endothelial nitric oxide synthase (eNOS) enzyme, is tightly coupled with cardiovascular health and circulation. To explore the role of BH4 in ME/CFS, serum samples of CFS patients (<i>n</i> = 32), CFS patients with OI only (<i>n</i> = 10; CFS + OI), and CFS patients with both OI and small fiber polyneuropathy (<i>n</i> = 12; CFS + OI + SFN) were subjected to BH4 ELISA. Interestingly, our results revealed that the BH4 expression is significantly high in CFS, CFS + OI, and CFS + OI + SFN patients compared to age-/gender-matched controls. Finally, a ROS production assay in cultured microglial cells followed by Pearson correlation statistics indicated that the elevated BH4 in serum samples of CFS + OI patients might be associated with the oxidative stress response. These findings suggest that the regulation of BH4 metabolism could be a promising target for understanding the molecular mechanism of CFS and CFS with OI. |
| first_indexed | 2024-03-11T03:39:56Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T03:39:56Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c3060de0d32b44d08d9b892e799c80f82023-11-18T01:40:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410871310.3390/ijms24108713Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot StudyCarl Gunnar Gottschalk0Ryan Whelan1Daniel Peterson2Avik Roy3Simmaron Research Institute, 948 Incline Way, Incline Village, NV 89451, USASimmaron Research Institute, 948 Incline Way, Incline Village, NV 89451, USASimmaron Research Institute, 948 Incline Way, Incline Village, NV 89451, USASimmaron Research Institute, 948 Incline Way, Incline Village, NV 89451, USAMyalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a multisystem chronic illness characterized by severe muscle fatigue, pain, dizziness, and brain fog. Many patients with ME/CFS experience orthostatic intolerance (OI), which is characterized by frequent dizziness, light-headedness, and feeling faint while maintaining an upright posture. Despite intense investigation, the molecular mechanism of this debilitating condition is still unknown. OI is often manifested by cardiovascular alterations, such as reduced cerebral blood flow, reduced blood pressure, and diminished heart rate. The bioavailability of tetrahydrobiopterin (BH4), an essential cofactor of endothelial nitric oxide synthase (eNOS) enzyme, is tightly coupled with cardiovascular health and circulation. To explore the role of BH4 in ME/CFS, serum samples of CFS patients (<i>n</i> = 32), CFS patients with OI only (<i>n</i> = 10; CFS + OI), and CFS patients with both OI and small fiber polyneuropathy (<i>n</i> = 12; CFS + OI + SFN) were subjected to BH4 ELISA. Interestingly, our results revealed that the BH4 expression is significantly high in CFS, CFS + OI, and CFS + OI + SFN patients compared to age-/gender-matched controls. Finally, a ROS production assay in cultured microglial cells followed by Pearson correlation statistics indicated that the elevated BH4 in serum samples of CFS + OI patients might be associated with the oxidative stress response. These findings suggest that the regulation of BH4 metabolism could be a promising target for understanding the molecular mechanism of CFS and CFS with OI.https://www.mdpi.com/1422-0067/24/10/8713ME/CFStetrahydrobiopterinorthostatic intolerancesmall fiber polyneuropathyendothelial NOSreactive oxygen species |
| spellingShingle | Carl Gunnar Gottschalk Ryan Whelan Daniel Peterson Avik Roy Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study International Journal of Molecular Sciences ME/CFS tetrahydrobiopterin orthostatic intolerance small fiber polyneuropathy endothelial NOS reactive oxygen species |
| title | Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study |
| title_full | Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study |
| title_fullStr | Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study |
| title_full_unstemmed | Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study |
| title_short | Detection of Elevated Level of Tetrahydrobiopterin in Serum Samples of ME/CFS Patients with Orthostatic Intolerance: A Pilot Study |
| title_sort | detection of elevated level of tetrahydrobiopterin in serum samples of me cfs patients with orthostatic intolerance a pilot study |
| topic | ME/CFS tetrahydrobiopterin orthostatic intolerance small fiber polyneuropathy endothelial NOS reactive oxygen species |
| url | https://www.mdpi.com/1422-0067/24/10/8713 |
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