Tomoe Fujita

Previous studies demonstrated that hamster sperm hyperactivation is suppressed by extracellular Na⁺ by lowering intracellular Ca²⁺ levels, and Na⁺/Ca²⁺-exchanger (NCX) specific inhibitors canceled the suppressive effects of extracellular Na⁺. These results suggest the involvement of NCX in the regulation of hyperactivation. However, direct evidence of the presence and functionality of NCX in hamster spermatozoa is still lacking. This study aimed to reveal that NCX is present and is functional in hamster spermatozoa. First, NCX1 and NCX2 transcripts were detected via RNA-seq analyses of hamster testis mRNAs, but only the NCX1 protein was detected. Next, NCX activity was determined by measuring the Na⁺-dependent Ca²⁺ influx using the Ca²⁺ indicator Fura-2. The Na⁺-dependent Ca²⁺ influx was detected in hamster spermatozoa, notably in the tail region. The Na⁺-dependent Ca²⁺ influx was inhibited by the NCX inhibitor SEA0400 at NCX1-specific concentrations. NCX1 activity was reduced after 3 h of incubation in capacitating conditions. These results, together with authors’ previous study, showed that hamster spermatozoa possesses functional NCX1 and that its activity was downregulated upon capacitation to trigger hyperactivation. This is the first study to successfully reveal the presence of NCX1 and its physiological function as a hyperactivation brake.

The importance of uric acid, the final metabolite of purines excreted by the kidneys and intestines, was not previously recognized, except for its role in forming crystals in the joints and causing gout. However, recent evidence implies that uric acid is not a biologically inactive substance and may exert a wide range of effects, including antioxidant, neurostimulatory, proinflammatory, and innate immune activities. Notably, uric acid has two contradictory properties: antioxidant and oxidative ones. In this review, we present the concept of “dysuricemia”, a condition in which deviation from the appropriate range of uric acid in the living body results in disease. This concept encompasses both hyperuricemia and hypouricemia. This review draws comparisons between the biologically biphasic positive and negative effects of uric acid and discusses the impact of such effects on various diseases.

Leukotriene B ₄ (LTB ₄ ) is a lipid mediator that acts as a potent chemoattractant for inflammatory leukocytes. Kidney fibrosis is caused by migrating inflammatory cells and kidney-resident cells. Here, we examined the role of the high-affinity LTB ₄ receptor BLT1 during development of kidney fibrosis in wild-type (WT) mice and BLT1 knockout (BLT1 ^-/- ) mice with unilateral ureteral obstruction (UUO). We found elevated expression of 5-lipoxygenase (5-LOX), which generates LTB ₄ , in the renal tubules of WT and BLT1 ^-/- UUO mice. Accumulation of immunoreactive type I collagen in UUO kidneys of WT mice increased over time; however, the increase was less prominent in BLT1 ^-/- mice. Accumulation of S100A4-positive fibroblasts also increased temporally in WT UUO kidneys, but was again less pronounced in those of BLT1 ^-/- mice. The same was true of mRNA encoding transforming growth factor-β (TGF)-β and fibroblast growth factor (FGF)-2. Finally, accumulation of F4/80-positive macrophages, which secrete TGF-β, also increased temporally in WT UUO and BLT1 ^-/- kidneys, but to a lesser extent in the latter. Following LTB ₄ stimulation in vitro , macrophages showed increased expression of mRNA encoding TGF-β/FGF-2 and Col1a1, whereas L929 fibroblasts showed increased expression of mRNA encoding α smooth muscle actin (SMA). Bone marrow (BM) transplantation studies revealed that the area positive for type I collagen was significantly smaller in BLT1 ^-/- -BM→WT UUO kidneys than in WT-BM→WT kidneys. Thus, LTB ₄ -BLT1 signaling plays a critical role in fibrosis in UUO kidneys by increasing accumulation of macrophages and fibroblasts. Therefore, blocking BLT1 may prevent renal fibrosis.