No abstract

Cysteine desulfurase IscS is required for cellular iron-sulfur protein maturation in eukaryotes and prokaryotes. In this study, we examined the effect of dietary iron intake on the expression in rat skeletal muscle of IscS in relation to 2 iron-sulfur proteins, cytosolic aconitase (c-aconitase) and mitochondrial aconitase (m-aconitase). Three groups of male weanling Wistar rats were used; 1 group was fed an iron-deficient diet (D), and the other 2 groups were pair-fed (P) or freely fed (C) a control (35 mg Fe/kg diet) diet for 1 or 2 wk. At the end of wk 1 and 2, the mitochondrial IscS protein levels in the skeletal muscle of iron-deficient rats had decreased to 45 and 50% of those of the control and pair-fed rats, respectively, whereas the IscS mRNA levels did not differ among the 3 groups, indicating that iron deficiency affected the expression of IscS protein at the post-transcriptional level. Iron deficiency caused a 55-76% reduction in c-aconitase activity and an approximately 50% reduction in the c-aconitase protein level. The m-aconitase activity and protein level in iron-deficient rats also declined to 50 and 58-64% of the control levels, respectively. Our results indicate that dietary iron modulates mitochondrial IscS protein and aconitase at the post-transcriptional level, and mitochondrial IscS may be associated with this regulation of aconitase in skeletal muscle.

Iron deficiency is the most common micronutrient deficiency in the world. Previous studies have shown that iron deficiency increases oxidative stress and decreases antioxidant enzymes, and studies of male infertility indicated that oxidative stress may affect male reproductive functions. The aim of this study was to investigate the effects of iron supplementation on spermatogenesis and testicular functions in iron-deficient rats. Three-week-old male Sprague Dawley (SD) rats were randomly divided into two groups: an iron-adequate control (AI group, 35 ppm FeSO4) and an iron-deficient group (ID group, <5 ppm FeSO4). After three weeks, the iron-deficient group was divided into an original iron-deficient group and five iron-supplemented groups, the latter fed diets containing different doses of FeSO4 (6, 12, 18, 24, and 35 ppm). After five weeks, blood and testis tissue were analyzed. We presented as median (interquartile range, IQR) for continuous measurements and compared their differences using the Kruskal–Wallis test followed by the Mann–Whitney U test among groups. The results showed that as compared with the AI group, the ID group had significantly lower serum testosterone and poorer spermatogenesis (The medians (QR) were 187.4 (185.6–190.8) of AI group vs. 87.5 (85.7–90.4) of ID group in serum testosterone, p < 0.05; 9.3 (8.8–10.6) of AI group vs. 4.9 (3.4–5.4) of ID group in mean testicular biopsy score (MTBS], p < 0.05); iron supplementation reversed the impairment of testis tissue. In the testosterone biosynthesis pathway, iron supplementation improved the lowered protein expressions of hydroxysteroid dehydrogenases caused by iron deficiency. Additionally, decreased activities of glutathione peroxidase and catalase, and increased cleaved-caspase 8 and caspase 3 expression, were found in the iron-deficient rats. The iron-supplemented rats that received > 12 ppm FeSO4 exhibited improvements in antioxidant levels. In conclusion, iron supplementation can abrogate testis dysfunction due to iron deficiency through regulation of the testicular antioxidant capacity.

Aim: Excessive glutamate release has been proposed to be involved in the pathogenesis of several neurological diseases. In this study, we investigated the effect of 4, 4a,5,8,-(phenylsulfonyl)-2-tosylisoquinolin-1(2H)-one), a novel synthetic compound, on glutamate release in rat cerebrocortical nerve terminals and explored the possible mechanism. Methods: The release of glutamate was evoked by the K + channel blocker 4-aminopyridine (4-AP) or the high external [K + ] and measured by one-line enzyme-coupled fluorometric assay. We also determined the loci at which HDT-1 impinges on cerebrocortical nerve terminals by using membrane potentialsensitive dye to assay nerve terminal excitability and depolarization, and Ca 2+indicator Fura-2 to monitor Ca 2+ influx. Results: HDT-1 inhibited the release of glutamate evoked by 4-AP and KCl in a concentration-dependent manner. HDT-1 did not alter the resting synaptosomal membrane potential or 4-APevoked depolarization. Examination of the effect of HDT-1 on cytosolic [Ca 2+ ] revealed that the diminution of glutamate release could be attributed to reduction in voltage-dependent Ca 2+ influx. Consistent with this, the HDT-1-mediated inhibition of glutamate release was significantly prevented in synaptosomes pretreated with the N-and P/Q-type Ca 2+ channel blocker ω-conotoxin MVIIC. Conclusion: In rat cerebrocortical nerve terminals, HDT-1 inhibits glutamate release through a reduction of voltage-dependent Ca 2+ channel activity and subsequent decrease of Ca 2+ influx into nerve terminals, rather than any upstream effect on nerve terminal excitability.

A new synthetic compound, 6-hydroxy-2-tosylisoquinolin-1(2H)-one (2-OH), was selected for immunopharmacological activity tests. The effects of 2-OH on human peripheral blood mononuclear cell (PBMC) proliferation were determined by tritiated thymidine uptake. Compared to phytohemagglutinin (PHA; 5 μg/mL) stimulation, 2-OH significantly enhanced PBMC proliferation in a dose-dependent manner. The 50% enhancement activity (EC50) for 2-OH was 4.4±0.1 μM. In addition, effects of 2-OH on interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in PBMC were determined by enzyme immunoassay. Results demonstrated that 2-OH stimulated IL-2 and IFN-γ production in PBMC. Data from reverse transcription-polymerase chain reaction (RT-PCR) and real-time PCR indicated that IL-2 and IFN-γ mRNA expression in PBMC could be induced by 2-OH. Therefore, 2-OH enhanced IL-2 and IFN-γ production in PBMC by modulation their gene expression. We suggest that 2-OH may be an immunomodulatory agent.