Thyroid hormone action on mitochondria

Measurements of fluorescence at >420 nm and extracted NADPH in mitochondria obtained from the livers of hypothyroid rats show that the addition of Pi, ADP and glutamate rapidly reduces over 90% of the total reducible intrinsic pyridine nucleotides in State 3, compared with 20% in normals. The total fluorescence intensity change and reducible NADP + is about twice normal in hypothyroid mitochondria. Adding 6–30 µM l -thyroxine to hypothyroid mitochondria in vitro decreases and delays the substrate-induced reduction of pyridine nucleotides, and excludes both NADP + from such reduction and NADPH from oxidation by added ADP + Pi, without changing the high NADP(H) content. The correcting actions of the hormone are rapidly reversed by albumin, probably by binding free hormone. Changes in respiration do not appear to account for these observations. There is indirect evidence for decreased phosphorylation of added ADP in hypothyroid mitochondria, and a correction by added hormone. The hormonal actions on NADP(H) redox reactions are not reproduced by 1 to 6 µM dinitrophenol in vitro . l -Thyroxine appears to specifically block the participation of NADP (H) in redox reactions in mitochondria from hypothyroid rats, perhaps by effecting a sequestration of the nucleotide, by inhibiting the pyridine nucleotide transhydrogenase, or by activating an energy-linked process that competes with transhydrogenation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44803/1/10863_2004_Article_BF00761448.pd

Why Should We Preserve Fishless High Mountain Lakes?

High mountain lakes are originally fishless, although many have had introductions of non-native fish species, predominantly trout, and recently also minnows introduced by fishermen that use them as live bait. The extent of these introductions is general and substantial often involving many lakes over mountain ranges. Predation on native fauna by introduced fish involves profound ecological changes since fish occupy a higher trophic level that was previously inexistent. Fish predation produces a drastic reduction or elimination of autochthonous animal groups, such as amphibians and large macroinvertebrates in the littoral, and crustaceans in the plankton. These strong effects raise concerns for the conservation of high mountain lakes. In terms of individual species, those adapted to live in larger lakes have suffered a higher decrease in the size of their metapopulation. This ecological problem is discussed from a European perspective providing examples from two study areas: the Pyrenees and the Western Italian Alps. Species-specific studies are urgently needed to evaluate the conservation status of the more impacted species, together with conservation measures at continental and regional scales, through regulation, and at local scale, through restoration actions, aimed to stop further invasive species expansions and to restore the present situation. At different high mountain areas of the world, there have been restoration projects aiming to return lakes to their native fish-free status. In these areas autochthonous species that disappeared with the introduction of fish are progressively recovering their initial distribution when nearby fish-free lakes and ponds are available

An Integrate-and-Fire Model for Synchronized Bursting in a Network of Cultured Cortical Neurons

It has been suggested that spontaneous synchronous neuronal activity is an essential step in the formation of functional networks in the central nervous system. The key features of this type of activity consist of bursts of action potentials with associated spikes of elevated cytoplasmic calcium. These features are also observed in networks of rat cortical neurons that have been formed in culture. Experimental studies of these cultured networks have led to several hypotheses for the mechanisms underlying the observed synchronized oscillations. In this paper, bursting integrate-and-fire type mathematical models for regular spiking (RS) and intrinsic bursting (IB) neurons are introduced and incorporated through a small-world connection scheme into a two-dimensional excitatory network similar to those in the cultured network. This computer model exhibits spontaneous synchronous activity through mechanisms similar to those hypothesized for the cultured experimental networks. Traces of the membrane potential and cytoplasmic calcium from the model closely match those obtained from experiments. We also consider the impact on network behavior of the IB neurons, the geometry and the small world connection scheme. Keywords: Integrate-and-fire, cultured cortical network, spontaneous synchronized oscillations

Histamine receptors in human fibroblasts: inositol phosphates, Ca2+, and cell growth

Histamine stimulated inositol phosphate formation by human skin fibroblasts. The effect of histamine was reduced but still readily apparent in the absence of extracellular Ca2+. Histamine caused a transient increase in intracellular free Ca2+ as detected by indo-1 and fura-2 fluorescence studies on cell populations and on individual cells. Similar increases were observed in the absence of extracellular Ca2+, indicating that the effect was primarily due to mobilization of Ca2+ from intracellular stores, presumably by inositol trisphosphate (IP3). The effects of histamine on phosphoinositide metabolism and intracellular Ca2+ were inhibited by pretreatment of the cells with phorbol esters, suggesting that the histamine receptor in fibroblasts is subject to feedback regulation by protein kinase C. Histamine inhibited the incorporation of [3H]-thymidine into DNA. The effects of histamine on inositol phosphate formation, intracellular Ca2+, and thymidine incorporation were blocked by the H1 receptor antagonist mepyramine. Our results indicate that human skin fibroblasts have H1 receptors coupled to the formation of inositol phosphates and mobilization of intracellular Ca2+. We suggest that this H1 receptor also mediates a block of the cell cycle and that histamine may play a physiological role in the regulation of fibroblast proliferation.</jats:p