Biochimica et biophysica acta
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Biochim. Biophys. Acta · May 2013
Pro-inflammatory cytokines modulate iron regulatory protein 1 expression and iron transportation through reactive oxygen/nitrogen species production in ventral mesencephalic neurons.
Both inflammatory processes associated with microglia activation and abnormal iron deposit in dopaminergic neurons are involved in the pathogenesis of Parkinson's disease (PD). However, the relationship between neuroinflammation and iron accumulation was not fully elucidated. In the present study, we aimed to investigate whether the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) released by microglia, could affect cellular iron transportation in primary cultured ventral mesencephalic (VM) neurons. ⋯ In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice, salicylate application could not block DMT1+IRE upregulation in dopaminergic neurons of substantia nigra. These results suggested that IL-1β and TNF-α released by microglia, especially under the condition of iron load, might contribute to iron accumulation in VM neurons by upregulating IRP1 and hepcidin levels through reactive oxygen/nitrogen species production. This might provide a new insight into unraveling that microglia might aggravate this iron mediated neuropathologies in PD.
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Biochim. Biophys. Acta · May 2013
Specific functioning of Cav3.2 T-type calcium and TRPV1 channels under different types of STZ-diabetic neuropathy.
Streptozotocin (STZ)-induced type 1 diabetes in rats leads to the development of peripheral diabetic neuropathy (PDN) manifested as thermal hyperalgesia at early stages (4th week) followed by hypoalgesia after 8weeks of diabetes development. Here we found that 6-7 week STZ-diabetic rats developed either thermal hyper- (18%), hypo- (25%) or normalgesic (57%) types of PDN. These developmentally similar diabetic rats were studied in order to analyze mechanisms potentially underlying different thermal nociception. ⋯ As a result, T-type window current was increased by several times under hyperalgesia partially underlying the increased resting [Ca(2+)]i observed in the hyperalgesic rats. At the same time Cav3.2-dependent Ca(2+) signaling was upregulated in all types of PDN. These findings indicate that alterations in functioning of Cav3.2 T-type and TRPV1 channels, specific for each type of PDN, may underlie the variety of pain syndromes induced by type 1 diabetes.
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Biochim. Biophys. Acta · May 2013
Stimulation of mitochondrial oxidative capacity in white fat independent of UCP1: a key to lean phenotype.
We are facing a revival of the strategy to counteract obesity and associated metabolic disorders by inducing thermogenesis mediated by mitochondrial uncoupling protein-1 (UCP1). Thus, the main focus is on the adaptive non-shivering thermogenesis occurring both in the typical depots of brown adipose tissue (BAT) and in UCP1-containing cells that could be induced in white adipose tissue (WAT). Because contribution of WAT to resting metabolic rate is relatively small, the possibility to reduce adiposity by enhancing energy expenditure in classical white adipocytes is largely neglected. ⋯ In this respect, new combination treatments may be designed using naturally occurring micronutrients (e.g. omega 3), reduced calorie intake or pharmaceuticals, exerting synergism in the induction of the mitochondrial OXPHOS capacity and stimulation of lipid catabolism in white adipocytes, and improving metabolic flexibility of WAT. The role of mutual interactions between adipocytes and immune cells contained in WAT in tissue metabolism should be better characterised. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.