Limits...
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.

Show MeSH

Related in: MedlinePlus

Coenzyme Q10 levels and mitochondrial membrane potential (ΔΨm) in blood mononuclear cells (BMCs) from fibromyalgia (FM) patients and healthy control subjects. (a) CoQ10 levels were measured with high-performance liquid chromatography, as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. (b) Mitochondrial membrane potential was analyzed in BMCs from control subjects and FM patients with flow cytometry, as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. *P < 0.001 between controls and FM patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2875645&req=5

Figure 1: Coenzyme Q10 levels and mitochondrial membrane potential (ΔΨm) in blood mononuclear cells (BMCs) from fibromyalgia (FM) patients and healthy control subjects. (a) CoQ10 levels were measured with high-performance liquid chromatography, as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. (b) Mitochondrial membrane potential was analyzed in BMCs from control subjects and FM patients with flow cytometry, as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. *P < 0.001 between controls and FM patients.

Mentions: CoQ10 levels, determined in BMCs isolated from 20 FM patients, were found to be about 40% lower than those in control cells (Figure 1a). To examine further the mitochondrial dysfunction in BMCs from FM patients, we determined the mitochondrial membrane potential (ΔΨm) with flow cytometry. Mitochondrial membrane potential was significantly reduced by about 36% in BMCs from FM patients (Figure 1b).


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)

Coenzyme Q10 levels and mitochondrial membrane potential (ΔΨm) in blood mononuclear cells (BMCs) from fibromyalgia (FM) patients and healthy control subjects. (a) CoQ10 levels were measured with high-performance liquid chromatography, as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. (b) Mitochondrial membrane potential was analyzed in BMCs from control subjects and FM patients with flow cytometry, as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. *P < 0.001 between controls and FM patients.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Coenzyme Q10 levels and mitochondrial membrane potential (ΔΨm) in blood mononuclear cells (BMCs) from fibromyalgia (FM) patients and healthy control subjects. (a) CoQ10 levels were measured with high-performance liquid chromatography, as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. (b) Mitochondrial membrane potential was analyzed in BMCs from control subjects and FM patients with flow cytometry, as described in Materials and Methods. Data represent the mean ± SD of three separate experiments. *P < 0.001 between controls and FM patients.
Mentions: CoQ10 levels, determined in BMCs isolated from 20 FM patients, were found to be about 40% lower than those in control cells (Figure 1a). To examine further the mitochondrial dysfunction in BMCs from FM patients, we determined the mitochondrial membrane potential (ΔΨm) with flow cytometry. Mitochondrial membrane potential was significantly reduced by about 36% in BMCs from FM patients (Figure 1b).

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