Introduction: Iron metabolism was found to be implicated in several cancers. Few epidemiologic studies; focusing on iron intake and lung cancer (LC), reported positive associations between heme iron and red meat. Based on estimates of iron contents in representative foods, we conducted the present study with the aim of analyzing dietary iron and its role on the incidence of LC in Uruguayan men,...

The effect of thrombin stimulation on actin organization in human platelets has been analyzed by using the DNase I inhibition assay, which is selective for unpolymerized and filamentous actin. The results provide biochemical evidence for the suggestion that stimulation leads to rapid polymerization of actin. The measurements also reveal changes in the polymerization state of actin occurring aft...

Impaired nitric oxide (NO), soluble guanylyl cyclase (sGC), and cyclic guanosine monophosphate (cGMP) signaling (NO-sGC-cGMP) has been implicated in the pathogenesis of diabetic vascular dysfunction. Efforts to directly target this signaling have led to the development of sGC agonists that activate the heme group of sGC (stimulators) or preferentially activate sGC when the heme is oxidized (act...

Strategies to use heme as a source of iron are key to the survival and virulence of many bacteria; inhibition of iron uptake pathways may be a new strategy to prevent bacterial infection. Corynebacterium diphtheriae is a Gram-positive, pathogenic bacterium that is the causative agent of diphtheria It utilizes proteins in heme uptake pathways to obtain required iron for survival and virulence. O...

Zinc protoporphyrin (ZnPP) is a normal metabolite that is formed in trace amounts during heme biosynthesis. The final reaction in the biosynthetic pathway of heme is the chelation of iron with protoporphyrin. During periods of iron insufficiency or impaired iron utilization, zinc becomes an alternative metal substrate for ferrochelatase, leading to increased ZnPP formation. Evidence suggests th...

The cytokine IL-12 is proposed to play a bridging role between innate and adaptive immunity. Here we demonstrate that IL-12 binds specifically to human neutrophils. This binding leads to a transient increase in 1) intracellular free calcium due to its release from membrane-enclosed stores and its influx from extracellular medium, 2) actin polymerization, and 3) tyrosine phosphorylation. IL-12 t...

A series of tubulysin analogs in which one of the stereogenic centers of tubuphenylalanine was eliminated were synthesized. All compounds were tested for antiproliferative activity towards ovarian cancer cells and for inhibition of tubulin polymerization. The dimethyl analogs were generally more active than the desmethyl analogs, and four analogs have tubulin polymerization IC(50) values simila...

Heme is a double-edged sword. On the one hand, it has pivotal role as prosthetic group of hemoproteins in many biological processes ranging from oxygen transport and storage to miRNA processing. other heme can transiently associate with proteins, thereby regulating biochemical pathways. During hemolysis, excess heme, which released into plasma, bind proteins regulate their activity function. Th...

A fungal alkaloid fungerin was found to arrest the cell cycle of Jurkat cells at the G2/M phase, then to induce apoptosis. Immunoblotting showed that fungerin led to hyperphosphorylation for Cdc25C and dephosphorylation of Cdc2, indicating that the compound arrests the cell cycle at the M phase. Moreover, fungerin inhibited the polymerization of microtubule proteins in vitro. It was concluded t...

Studies have indicated that specific heme delivery to apocytochrome c is a critical feature of the cytochrome c biogenesis pathways called system I and II. To determine directly the heme requirements of each system, including whether other metal porphyrins can be incorporated into cytochromes c, we engineered Escherichia coli so that the natural system I (ccmABCDEFGH) was deleted and exogenous ...