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101.
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The mitochondrial inner membrane anion channel (IMAC) is a transport pathway which is believed to be involved in mitochondrial volume homeostasis. The protein, however, has not been identified. In this paper, we examine the relationship between IMAC and the adenine nucleotide translocator. Many inhibitors of the adenine nucleotide translocase are shown to block IMAC, including Cibacron blue 3GA, bromcresol green, alizarin red S, agaric acid, palmitoyl-CoA, and the fluorescein derivatives erythrosin B, erythrosin isothiocyanate, rose bengal, and eosin Y. The following evidence suggests that Cibacron blue, agaric acid, and palmitoyl-CoA inhibit by binding to a common site. 1) They all only partially block the transport of small anions such as Cl-, NO3-, and HCO3-, but completely block the transport of larger anions such as malonate. 2) They decrease the IC50 values of each other in a manner consistent with competitive binding. 3) N-Ethylmaleimide decreases their IC50 values by a similar extent. 4) Inhibition by all shows no dependence on matrix pH and only a small dependence on medium pH. It is suggested that these agents may selectively bind to an open state of IMAC and inhibit by decreasing its conductance. The physiological nucleotides CoA, NAD+, NADH, NADP+, NADH, and ATP do not inhibit; in fact, IMAC is shown to transport ATP. Despite these similarities between IMAC and the adenine nucleotide translocase, IMAC appears to be a separate entity, since some of the IC50 values differ by up to 8-fold, and carboxyatracyloside, the most selective inhibitor of the adenine nucleotide translocase, has no effect on IMAC. In addition, IMAC is also able to transport AMP, while the adenine nucleotide translocase does not. 相似文献
103.
MH Maslowska AD Sniderman LD MacLean K Cianflone 《Canadian Metallurgical Quarterly》1993,34(2):219-228
The initial suspicion that obesity increases coronary risk has been much sharpened with the demonstration that risk is more tightly linked to abdominal than to peripheral obesity, and tighter yet again when the mass of omental adipose tissue is taken into account. These data suggest that important metabolic differences might exist between adipocytes from different regions, and indeed, it has long been appreciated that triacylglycerol hydrolysis can be stimulated to a greater extent in omental than in subcutaneous adipocytes. The present study focuses on triacylglycerol synthesis in human subcutaneous and omental adipocytes, a process which, by contrast, has received relatively little attention. Experiments were done on adipose tissue removed at laparotomy and on cultured preadipocytes. With the former, triacylglycerol synthesis was measured in the presence and absence of oleate added to the medium using radiolabeled glucose and oleate as tracers. The results demonstrate that under all conditions examined triacylglycerol synthesis in subcutaneous adipose tissue exceeded that in deep omental adipose tissue. To study the cells in more detail, preadipocytes were cultured and triacylglycerol synthesis was examined again under basal conditions and with stimulation with insulin and acylation stimulating protein (ASP). Under basal conditions, particularly when oleate was added to the medium, clear differences were present such that triacylglycerol synthesis was substantially greater in subcutaneous preadipocytes than in omentally derived preadipocytes. These differences were more pronounced when the cells were stimulated with either insulin or acylation stimulating protein. Overall, triacylglycerol synthetic capacity in subcutaneous tissue exceeded that in omental tissue. As a consequence, omental tissue as compared to subcutaneous adipose tissue would have a limited capacity to prevent fatty acids from reaching the liver and stimulating hepatic lipoprotein synthesis. 相似文献
104.
SC Langley GW Rickett A Hunt FJ Kelly AD Postle DA York 《Canadian Metallurgical Quarterly》1993,45(3):543-551
The biochemical maturation of the lung in late gestation and in the young animal is regulated by glucocorticoids. The present study was aimed at dissociating the different glucocorticoid receptor sites involved in these regulatory functions. The obese Zucker rat was selected as a model for this study as it exhibits hypersensitivity to glucocorticoid hormone action by virtue of its elevated receptor numbers and activity. Two synthetic steroid analogues were administered to obese animals; RU28362, a specific type II receptor agonist, and the type II antagonist RU486. RU28362 promoted a strong catabolic effect, which was associated with reduced food intake and the abolition of growth in the rats. The agonist, RU28362, attenuated developmental increases in antioxidant enzyme activities, and altered the growth of the tissue. At the age studied, development of the lung phosphatidylcholine (PC) system was almost complete, but RU28362 increased disaturated PC 16:0/16:0 concentrations by almost 2-fold, and altered the molecular composition of total pulmonary PC. RU486 attenuated the growth of the rats and reduced their food intake. Treatment with the type II antagonist attenuated lung growth and increased the activities of pulmonary copper zinc (Cu/Zn) and manganese (Mn) superoxide dismutases. RU486 had no effect on lung PC concentrations and molecular composition. The data suggest a role for type I glucocorticoid receptors in the regulation of the antioxidant enzyme system in the lung, as type II antagonism will channel endogenous glucocorticoid binding to the type I site. Type II receptor binding would appear to play a role in regulating the lung PC content. 相似文献
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The behavioral disturbances of 16 nursing home patients with a history of sundowning behaviour and dementia were treated with light therapy instead of psychopharmacological medication. After the withdrawal of the before established medication a very individual, heterogenous deterioration of the symptoms was noted. A significant improvement of the behaviour was not found by light therapy in any patient. The problems in practical handling and possible consequences of further investigation are discussed. 相似文献
110.