Guillermo Lopez Lluch | Universidad Pablo de Olavide (original) (raw)

Papers by Guillermo Lopez Lluch

Medicina-buenos Aires, 2016

La Nefritis Lupica (NL) es mas frecuente en mujeres. Se reconoce que madres con Lupus Eritematoso... more La Nefritis Lupica (NL) es mas frecuente en mujeres. Se reconoce que madres con Lupus Eritematoso Sistemico (LES) confieren mayor riesgo al desarrollo de esta entidad en sus hijos. Esta transmision se debe a la impronta genomica y/o al genotipo materno sobre el desarrollo prenatal. En este estudio se identificaron variantes de los sistemas PTPN22, VDR y TNF, asociadas a NL pediatrica (NLp). Se investigo la asociacion de marcadores en 64 familias: 46 trios (Caso/Padre- Madre) y 18 duos (Caso/Madre). Se genotipificaron los SNPs rs2476601 [A/G] de PTPN22; rs361525 [A/G] y rs1800629 [A/G] de TNF; TaqI [rs731236 A/G], ApaI [rs7975232 A/C], BsmI [rs1544410 C/T] y FokI [rs2228570 A/G] de VDR mediante RT-PCR. Se estimo el efecto de la sobretransmision del alelo de riesgo de padres a hijos. Se estimo el efecto genetico de los SNPs sobre los ninos (R1 y R2) y tambien se estudiaron la influencia genetica materna (S1 y S2) y la impronta materna (Im). Se observo que el alelo A de rs2476601 en PT...

Bratislava Medical Journal

BACKGROUND: SARS-CoV-2 infection is associated with infl ammation, decrease in antioxidants and o... more BACKGROUND: SARS-CoV-2 infection is associated with infl ammation, decrease in antioxidants and oxidative damage. We aimed to investigate whether ubiquinol, reduced form of coenzyme Q 10 (CoQ 10), with mountain spa rehabilitation (MR) will contribute to recovering of patients with post-COVID-19 syndrome. METHODS: The study included 36 patients on MR lasting 16-18 days. Twenty-two patients were supplemented with ubiquinol 2x100 mg/day (MRQ), 14 underwent MR without supplementation. The control group consisted of 15 healthy volunteers. Concentrations of total CoQ 10 (ubiquinone + ubiquinol) , α-and γ-tocopherol were determined in platelets (PLT), in blood and plasma, also β-carotene was determined. Plasma concentration of thiobarbituric acid-reactive substances (TBARS) was used as the oxidative stress marker. Clinical symptoms were evaluated by questionnaire. RESULTS: MRQ group showed a signifi cant increase in CoQ 10 , namely in PLT by 68 %, in blood by 194 %, and in plasma by 232 %. In MR group, CoQ 10 stayed unchanged. In both groups, the initially increased concentrations of tocopherols in PLT returned nearly to the control values. β-carotene levels decreased in both groups while TBARS decreased slightly in the MRQ group. More clinical symptoms disappeared in the MRQ group. CONCLUSION: Accelerated recovery of patients with post-COVID-19 syndrome was proven after mountain spa rehabilitation and ubiquinol supplementation. Increased systemic and cellular CoQ 10 concentration alleviated clinical symptoms and improved antioxidant protection of the patients. We draw attention to the importance of monitoring and ensuring adequate levels of CoQ 10 in post-COVID-19 syndrome (Tab. 2, Fig. 1, Ref.

ABSTRACTImpaired spermatogenesis and male infertility are common manifestations of mitochondrial ... more ABSTRACTImpaired spermatogenesis and male infertility are common manifestations of mitochondrial diseases, but the underlying mechanisms are unclear. Here we show that mice deficient for PARL, the mitochondrial rhomboid protease, a recently reported model of Leigh syndrome, develop postpubertal testicular atrophy caused by arrested spermatogenesis and germ cell death independently of neurodegeneration. Genetic modifications of PINK1, PGAM5, and TTC19, three major substrates of PARL with important roles in mitochondrial homeostasis, do not reproduce or modify this phenotype. PARL deficiency in testis mitochondria leads to severe mitochondrial electron transfer chain defects, alterations in Coenzyme Q biosynthesis and redox status, and abrogates GPX4 expression specifically in spermatocytes leading to massive ferroptosis, an iron-dependent regulated cell death modality characterized by uncontrolled lipid peroxidation. Thus, mitochondrial defects can initiate ferroptosisin vivoin speci...

Biochimica et Biophysica Acta (BBA) - Biomembranes, 2005

Molecular Cancer Therapeutics, 2008

Securin, the natural inhibitor of sister chromatid untimely separation, is a protooncogene overex... more Securin, the natural inhibitor of sister chromatid untimely separation, is a protooncogene overexpressed in tumors. Its protein levels correlate with malignancy and metastatic proneness. Dicoumarol, a long-established oral anticoagulant, is a new Hsp90 inhibitor that represses PTTG1/ Securin gene expression and provokes apoptosis through a complex trait involving both intrinsic and extrinsic pathways. Dicoumarol activity as an Hsp90 inhibitor is confirmed by smaller levels of Hsp90 clients in treated cells and inhibition of in vivo heat shock luciferase activity recovery assays. Likewise, established Hsp90 inhibitors (17-allylamino-geldanamycin and novobiocin) repress PTTG1/Securin gene expression. Also, overexpression of human Hsp90 in yeast makes them hypersensitive to dicoumarol. Both apoptosis and PTTG1/Securin gene repression exerted by dicoumarol in cancer cells are independent of three of the most important signaling pathways affected by Hsp90 inhibition: nuclear factor-KB, p53, or Akt/protein kinase B signaling pathways. However, effects on PTTG1/Securin could be partially ascribed to inhibition of the Ras/Raf/extracellular signalregulated kinase pathway. Overall, we show that expression of PTTG1/Securin gene is Hsp90 dependent and that dicoumarol is a bona fide Hsp90 inhibitor. These findings are important to understand the mode of action of Hsp90 inhibitors, mechanisms of action of dicoumarol, and Securin overexpression in tumors.

Sarcopenia is known as a progressive muscle wasting produced as years accumulate and characterize... more Sarcopenia is known as a progressive muscle wasting produced as years accumulate and characterized by a progressive loss of muscle mass and strength, increase of muscle fat and progressive decline of functional capacity. This process produces important and severe effects on quality of life in elderly people since sarcopenia is the most frequent cause of discapacity, dependency and increase or morbi-mortality. In the present review we analyze the different etiological factors and the prevention and treatment strategies against sarcopenia. One of the main strategies is the strength training that, added to an adequate nutrition, plays a primordial role in prevention and progression of sarcopenia.

RESUMEN
Se conoce como sarcopenia al progresivo deterioro muscular que se produce con el paso de los años y que se caracteriza por una pérdida progresiva de fuerza y masa musculares, aumento de la grasa muscular y el deterioro progresivo de la capacidad funcional. Este proceso tiene importantes repercusiones en la calidad de vida de las personas mayores, ya que es causa frecuente de discapacidad, dependencia y aumento de la morbimortalidad. En la presente revisión bibliográfica del tema, analizamos los diferentes factores etiológi- cos y las estrategias de prevención y tratamiento de la sarcopenia, entre las que el ejercicio, y en particular el entrenamiento de fuerza, junto con una alimentación adecuada, desempeñan un papel primordial.

Proceedings of the National Academy of Sciences

The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions i... more The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that Parl ablation in mouse causes a necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice with conditional PARL deficiency in the nervous system, but not in muscle, develop a similar phenotype as germline Parl KOs, demonstrating the vital role of PARL in neurological homeostasis. Genetic modification of two major PARL substrates, PINK1 and PGAM5, do not modify this severe neurological phenotype. Parl−/− brain mitochondria are affected by progressive ultrastructural changes and by defects in Complex III (CIII) activity, coenzyme Q (CoQ) biosynthesis, and mitochondrial calcium metabolism. PARL is necessary for the stable expression of TTC19, which is required for CIII activity, and of COQ4, which is essential in CoQ biosynthesis. Thus, P...

Dose-Response

This study aimed to compare the effect of high-intensity interval training (HIIT) with additional... more This study aimed to compare the effect of high-intensity interval training (HIIT) with additional whole-body vibration (WBV) on body composition and lipid profile in obese/overweight adults on a hypocaloric diet. Forty adults were randomly assigned to (a) HIIT and vibration and hypocaloric diet (HIITWBV, n = 13), (b) HIIT and diet (HIIT, n = 14), and (c) diet only (control [CON], n = 13). High-intensity interval training WBV participants trained 3 times per week for 8 weeks (6 sets × 1 minute of HIIT, cycling at 90% heart rate peak followed by 1 minute of interset vibration, at a frequency of 18 Hz increasing until 25 Hz with a peak-to-peak displacement of 4 mm. Training volume increased 1 set every 2 weeks until 10 sets). The HIIT group performed HIIT training followed by 2 minutes of passive recovery, while the CON continued with their daily activities combined with calorie restriction. Body composition (body fat and fat-free mass) and biochemical indices (glucose, total cholester...

Science & Sports

Summary Objective To determine the influence of the level of physical activity on physical fitnes... more Summary Objective To determine the influence of the level of physical activity on physical fitness, body composition and lipid profile and further explore the associations between fitness with these health outcomes in a population of overweight/obese adults. Methods Forty overweight/obesity participants with a caloric intake between a negative balance of 500 kcal/day and their estimated required energy intake were classified according to their level of physical activity. Anthropometric (weight and height), body composition (waist-to-hip ratio, percentage of body fat and fat-free mass), clinical measurements (blood pressure), physical fitness (cardiorespiratory fitness – 6MWT –, handgrip strength and lower-limb muscle strength – MVC –) and lipid profile (total cholesterol – TC –, low – LDL – and high-density lipoprotein cholesterol – HDL –, triglyceride – TG –, and plasma glucose) were determined. Results Significant differences in MVC and fat-free mass were found between participants with different physical level. Significant associations between all the body composition measures and the strength-related variables (handgrip and MVC) in both physical activity categories also were found. In addition, associations between triglycerides, LDL and total cholesterol with muscle strength and cardiorespiratory fitness were observed only in the low physical activity group. Moreover, MVC explained up to 39% of the variance in metabolic syndrome in those with a moderate level of physical activity. Conclusions Correlations between physical fitness (especially in strength) and health risk factors depending on the level of physical activity were found.

Revista Andaluza de Medicina del Deporte, 2013

Influence of functional capacity on lipid profile, muscle damage and biochemical profile among co... more Influence of functional capacity on lipid profile, muscle damage and biochemical profile among community-dwelling elderly-people Objective. To analyze the influence of functional capacity on the biochemical profile and muscle damage and to test the level of relationship between these variables among community-dwelling elderly people. Method. A cross-sectional, observational study with 43 participants (19 males and 24 women) was performed. Functional capacity (including 6MWT, TUG test, CST test and Hand grip strength test), and biochemical profile (including total cholesterol, HDL, LDL, triglycerides, glucose, GOT, GPT, creatine and CK) were assessed. Differences on biochemical profile-related variables regarding the functional capacity level were analyzed. The level of relationship between the variables comprising these two domains was also assessed. Results. Those participants with a better results in functional capacity variables also achieved the better results in regard of the biochemical parameters measured (p < 0,05). These differences were also maintained after a gender-based analysis. Moreover, relationships between muscle damage and functional capacity variables were also achieved. Conclusion. This study shows the influence of the functional capacity on the biochemical parameters (mostly associated to cardiovascular and metabolic diseases) along with the influence that such variables have on the muscle damage and suggest the needed on the implementation of both aerobic and strength training for elderly.

Protoplasma, 1995

TPA or 1,25-dihydroxyvitamin D3 (calcitriol). Induction with TPA was in parallel with a modulatio... more TPA or 1,25-dihydroxyvitamin D3 (calcitriol). Induction with TPA was in parallel with a modulation of transmembrane redox system. After addition of 2 ng/ml TPA, transient increases in ferricyanide rednctase activity, NAD(H) intracellular levels and short-term response of NAD(H) to 0.4 mM ferricyanide were observed. The role of ascorbate on the differentiation induced by calcitriol also was studied. When HL-60 ceils were exposed to 10-8 M calcitriol in the presence of 0.2 mM ascorbate, specific differentiation markers as NBT reduction or surface antigen CD1 lb increased significantly with respect to values obtained from treatments with calcitriol alone.

Protoplasma, 2001

Summary Ascorbate has been related to the differentiation of several mesenchymal cells including ... more Summary Ascorbate has been related to the differentiation of several mesenchymal cells including haematopoietic cells. We have previously demonstrated that ascorbate enhances the activity of 1a,25-dihydroxyvitamin D3 (1a,25(OH)2D3) on monocytic differentiation of HL-60 cells. Here, we show that ascorbate-mediated modification of cellular redox state and AP-1 (activating protein-1) DNA binding during early phases are related to the enhancing effect of

… of bioenergetics and …, 1997

Serum provides cultured cells with survival factors required to maintain growth. Its withdrawal i... more Serum provides cultured cells with survival factors required to maintain growth. Its withdrawal induces the development of programmed cell death. HL-60 cells were sensitive to serum removal, and an increase of lipid peroxidation and apoptosis was observed. Long-term ...

… et Biophysica Acta (BBA …, 2005

Coenzyme Q (Q) is an essential factor in the mitochondrial electron chain but also exerts importa... more Coenzyme Q (Q) is an essential factor in the mitochondrial electron chain but also exerts important antioxidant functions in the rest of cell membranes of aerobic organisms. However, the mechanisms of distribution of Q among cell membranes are largely unclear. The aim of the present work is to study the mechanisms of distribution of endogenous Q 10 and exogenous Q 9 among cell membranes in human HL-60 cells. Endogenous Q 10 synthesized using the radiolabelled precursor [ 14 C]-pHB was first detected in mitochondria, and it was later incorporated into mitochondria-associated membranes and endoplasmic reticulum (ER). Plasma membrane was the last location to incorporate [ 14 C]-Q 10. Brefeldin A prevented Q 10 incorporation in plasma membrane. Exogenous Q 9 was preferably accumulated into the endo-lysosomal fraction but a significant amount was distributed among other cell membranes also depending on the brefeldin-A-sensitive endomembrane system. Our results indicate that mitochondria are the first location for new synthesized Q. Exogenous Q is mainly incorporated into an endolysosomal fraction, which is then rapidly incorporated to cell membranes mainly to MAM and mitochondria. We also demonstrate that both endogenous and dietary Q is distributed among endomembranes and plasma membrane by the brefeldin A-sensitive endo-exocytic pathway.

Mechanisms of Ageing and Development