Using a modular library format in conjunction with cell viability (MTS) and flow cytometry assays, 90 cationic complexes [AuPL] n+ (P = phosphine ligand; L = thiourea derivative or chloride) were studied for their antiproliferative activity in CD8 + T lymphocyte cells.

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Estrogen has numerous direct and indirect effects on mitochondrial and cerebral vascular function but the mechanisms are not fully understood. We and others have found enhanced mitochondrial respiration in female compared with male rats and mice, and in young rats exposed to ovariectomy (OVX) prior to sexual maturity followed by 3 wk of estradiol/placebo treatment. However, the effects of delayed hormone replacement therapy after OVX are unclear in more mature rats. The aims of this study were 1) to determine the effects of estrogen on mitochondrial functioning of Sprague Dawley rats undergoing OVX after reaching sexual maturity (6 wk), then exposed to a delayed treatment administered between weeks 11 and 14 of 0.5 mg of 17 β‐estradiol (E) or placebo (P); 2) to determine the activity of citrate synthase, a key mitochondrial protein involved in ATP production, of isolated cerebral arteries of male and female C57BL/6J mice; and 3) to elucidate the mechanisms of estrogen on isolated primary mouse brain microvascular endothelial cells (MBMEC). There were no differences in body weights of 6 wk old rats immediately after OVX (P: 167.3 ± 3 g; E: 163.2 ± 3.4 g), whereas estrogen treatment resulted in a significantly lower body weights by the end of 14 wk in E (287.5 ± 6.4 g) compared with the P treated group (347.2 ± 8.3 g). There was significantly greater uterus weight/tibia length ratio in E group (0.119 ± 0.011) compared with P (0.025 ± 0.002). Basal respiration and proton leak measured with the Seahorse Bioscience Analyzer were significantly increased in E compared with P group (E: 341 ± 45.52; P: 154 ± 52; E: 250.9 ± 36.9; and P: 101.7 ± 42.2, respectively, pmol/min/mg protein), as well as the respiratory control ratio in the presence of 0.5 mM N,N,N′,N′‐tetramethyl‐p‐phenylenediamine (TMPD) + 2mM ascorbate + 1 mM ADP. In addition, we found a greater citrate synthase activity in arteries isolated from female mice (1.7e‐004 ± 4.7e‐005) compared with males (8e‐005 ± 2.5e‐005). Estradiol treatment (100 nM) resulted in an increase in the extracellular acidification rate (ECAR) vs. oxygen consumption rate (OCR) values (70.3 ± 16.7 and 157 ± 46.6) of isolated MBMEC, indicative of the energy phenotype for these cells, compared with vehicle treatment (11.4 ± 5.5 and 132.4 ± 22.7), which was further increased in the presence of TMPD + ascorbate + ADP (vehicle: 201.3 ± 55.7 and 383.8 ± 77; estradiol: 216.5 ± 47 and 517.1 ± 85.3). Our results indicate that estrogen enhances mitochondrial respiration upon a delayed administration protocol in rats, increases citrate synthase activity in female mice, and energizes MBMEC under baseline conditions and in the presence of the electron donor TMPD. Thus, promotes enhanced mitochondrial function in cerebral vascular cells of mice and rats.Support or Funding InformationThis work was supported by National Institutes of Health grants [HL‐077731; HL093554 (DWB), and NS094834 (PVK)], Louisiana Board of Regents Endowed Chairs for Eminent Scholars program (DWB), American Heart Association grants [15POST23040005; 17SDG33410366 (IR), and 14SDG20490359 (PVK)].This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.