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Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease.

Cordero MD, De Miguel M, Moreno Fernández AM, Carmona López IM, Garrido Maraver J, Cotán D, Gómez Izquierdo L, Bonal P, Campa F, Bullon P, Navas P, Sánchez Alcázar JA - Arthritis Res. Ther. (2010)

Bottom Line: Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells.We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients.Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, Ctra, de Utrera, km, 1, ISCIII, Sevilla 41013, Spain. mdcormor@upo.es

ABSTRACT

Introduction: Fibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia.

Methods: We studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q10 levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells.

Results: We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy.

Conclusions: These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.

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Related in: MedlinePlus

Autophagic genes expression. Expression levels of BECLIN 1 (a) and MAP-LC3 (b) transcripts in blood mononuclear cells (BMCs) from control and fibromyalgia (FM) patients were assessed with real-time polymerase chain reaction (PCR), as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. *P < 0.001 between controls and FM patients. (c) Correlation of CoQ10 levels and BECLIN 1 and MAP-LC3 expression levels in BMCs from FM patients.
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Figure 5: Autophagic genes expression. Expression levels of BECLIN 1 (a) and MAP-LC3 (b) transcripts in blood mononuclear cells (BMCs) from control and fibromyalgia (FM) patients were assessed with real-time polymerase chain reaction (PCR), as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. *P < 0.001 between controls and FM patients. (c) Correlation of CoQ10 levels and BECLIN 1 and MAP-LC3 expression levels in BMCs from FM patients.

Mentions: In addition, we analyzed the expression of genes involved in autophagic processes, such as BECLIN 1 and MAP-LC3. Figure 5a and 5b show that autophagic genes were overexpressed in BMCs of five of the eight patients tested as compared with controls. FM patients with increased expression of autophagic genes were those with a most pronounced CoQ10 deficiency (P3, P5, P6, P7, P8). A negative correlation was seen between the expression of autophagic genes and CoQ10 levels (r = -0.80, P < 0.01 for BECLIN 1, and r = -0.76, P < 0.001 for MAP-LC3) (Figure 5c).


Mitochondrial dysfunction and mitophagy activation in blood mononuclear cells of fibromyalgia patients: implications in the pathogenesis of the disease.

Cordero MD, De Miguel M, Moreno Fernández AM, Carmona López IM, Garrido Maraver J, Cotán D, Gómez Izquierdo L, Bonal P, Campa F, Bullon P, Navas P, Sánchez Alcázar JA - Arthritis Res. Ther. (2010)

Autophagic genes expression. Expression levels of BECLIN 1 (a) and MAP-LC3 (b) transcripts in blood mononuclear cells (BMCs) from control and fibromyalgia (FM) patients were assessed with real-time polymerase chain reaction (PCR), as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. *P < 0.001 between controls and FM patients. (c) Correlation of CoQ10 levels and BECLIN 1 and MAP-LC3 expression levels in BMCs from FM patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875645&req=5

Figure 5: Autophagic genes expression. Expression levels of BECLIN 1 (a) and MAP-LC3 (b) transcripts in blood mononuclear cells (BMCs) from control and fibromyalgia (FM) patients were assessed with real-time polymerase chain reaction (PCR), as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. *P < 0.001 between controls and FM patients. (c) Correlation of CoQ10 levels and BECLIN 1 and MAP-LC3 expression levels in BMCs from FM patients.
Mentions: In addition, we analyzed the expression of genes involved in autophagic processes, such as BECLIN 1 and MAP-LC3. Figure 5a and 5b show that autophagic genes were overexpressed in BMCs of five of the eight patients tested as compared with controls. FM patients with increased expression of autophagic genes were those with a most pronounced CoQ10 deficiency (P3, P5, P6, P7, P8). A negative correlation was seen between the expression of autophagic genes and CoQ10 levels (r = -0.80, P < 0.01 for BECLIN 1, and r = -0.76, P < 0.001 for MAP-LC3) (Figure 5c).

Bottom Line: Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells.We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients.Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy.

View Article: PubMed Central - HTML - PubMed

Affiliation: Centro Andaluz de Biología del Desarrollo (CABD), Universidad Pablo de Olavide-CSIC, Ctra, de Utrera, km, 1, ISCIII, Sevilla 41013, Spain. mdcormor@upo.es

ABSTRACT

Introduction: Fibromyalgia is a chronic pain syndrome with unknown etiology. Recent studies have shown some evidence demonstrating that oxidative stress may have a role in the pathophysiology of fibromyalgia. However, it is still not clear whether oxidative stress is the cause or the effect of the abnormalities documented in fibromyalgia. Furthermore, the role of mitochondria in the redox imbalance reported in fibromyalgia also is controversial. We undertook this study to investigate the role of mitochondrial dysfunction, oxidative stress, and mitophagy in fibromyalgia.

Methods: We studied 20 patients (2 male, 18 female patients) from the database of the Sevillian Fibromyalgia Association and 10 healthy controls. We evaluated mitochondrial function in blood mononuclear cells from fibromyalgia patients measuring, coenzyme Q10 levels with high-performance liquid chromatography (HPLC), and mitochondrial membrane potential with flow cytometry. Oxidative stress was determined by measuring mitochondrial superoxide production with MitoSOX and lipid peroxidation in blood mononuclear cells and plasma from fibromyalgia patients. Autophagy activation was evaluated by quantifying the fluorescence intensity of LysoTracker Red staining of blood mononuclear cells. Mitophagy was confirmed by measuring citrate synthase activity and electron microscopy examination of blood mononuclear cells.

Results: We found reduced levels of coenzyme Q10, decreased mitochondrial membrane potential, increased levels of mitochondrial superoxide in blood mononuclear cells, and increased levels of lipid peroxidation in both blood mononuclear cells and plasma from fibromyalgia patients. Mitochondrial dysfunction was also associated with increased expression of autophagic genes and the elimination of dysfunctional mitochondria with mitophagy.

Conclusions: These findings may support the role of oxidative stress and mitophagy in the pathophysiology of fibromyalgia.

Show MeSH
Related in: MedlinePlus