RESUMEN
Glutathione deficiency is commonly associated with mitochondrial complex I dysfunction and loss of viability in neurones, but not in glia. In order to address the possible mechanism responsible for this cellular difference, the regulation of mitochondrial complex I expression by glutathione depletion was investigated in glial cells. Incubation of rat-cultured astrocytes and C6 glioma cells with the specific gamma-glutamylcysteine synthetase inhibitor L-buthionine-(S:,R:)-sulfoximine (L-BSO; 0.1-1 mM) decreased the total specific content of glutathione in a dose- and time-dependent fashion. Northern blot analyses revealed that glutathione deficiency caused by L-BSO (0.1 mM) was associated with a twofold enhancement in complex I regulatory subunit ND6 (mitochondrially encoded) mRNA expression after 24-72 h. This effect was accompanied by a twofold increase in complex-I activity at 72 h in L-BSO-treated cells, as compared with control cells, but complex II-III, complex IV and citrate synthase activities were unaltered. It is suggested that the oxidative stress caused by glutathione depletion in glial cells would up-regulate complex-I activity by enhancing the expression of the mitochondrially encoded regulatory subunit. These results could offer further insight into the different degree of cellular susceptibility observed in glial vs. neuronal cells against oxidative stress.
Asunto(s)
Astrocitos/enzimología , Butionina Sulfoximina/farmacología , Regulación Enzimológica de la Expresión Génica , Glutatión/metabolismo , NADH NADPH Oxidorreductasas/genética , Neuroglía/enzimología , Animales , Animales Recién Nacidos , Células Cultivadas , Citrato (si)-Sintasa/genética , Complejo I de Transporte de Electrón , Complejo II de Transporte de Electrones , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glioma , Complejos Multienzimáticos/genética , Oxidorreductasas/genética , Prosencéfalo/citología , Prosencéfalo/enzimología , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Succinato Deshidrogenasa/genética , Células Tumorales CultivadasRESUMEN
OBJECTIVE: To report the effects of 2 regimens of hormone replacement therapy during the postmenopausal period on the profile of the major lipoprotein subfractions (HDL, LDL, and VLDL). METHODS: We carried out a cohort study in 38 postmenopausal patients who were starting their hormone replacement therapy due to gynecological indications, for a period of 12 weeks. Analysis of lipoprotein subclasses was performed through nuclear magnetic resonance spectroscopy. RESULTS: Hormone replacement therapy cause an increase in the proportion of larger subfractions of VLDL and HDL (p=0.008 and 0.03, respectively) and in the proportion of larger particles of VLDL due to a 36% increase in the levels of larger particles (p=0.004), concomitantly with a 15% reduction in the levels of smaller particles (p=0.04). In regard to HDL, the increase occurred only a 17% increase in the levels of larger particles (p=0.002). No significant change occurred in the distribution pattern of LDL subfractions. CONCLUSION: The proportion of larger subfractions of VLDL and HDL increases after hormone replacement therapy. The increase in the proportion of larger particles of VLDL occurs due to an increase in the levels of the larger subclasses concomitantly with a reduction in the smaller particles. However, an increase in the proportion of larger particles of HDL occurs only due to an increase in the levels of the larger subfractions.