The Roles of Sodium-Independent Inorganic Phosphate Transporters in Inorganic Phosphate Homeostasis and in Cancer and Other Diseases

Inorganic phosphate (Pi) is an essential nutrient for the maintenance of cells. In healthy mammals, extracellular Pi is maintained within a narrow concentration range of 0.70 to 1.55 mM. Mammalian cells depend on Na+/Pi cotransporters for Pi absorption, which have been well studied. However, a new type of sodium-independent Pi transporter has been identified. This transporter assists in the absorption of Pi by intestinal cells and renal proximal tubule cells and in the reabsorption of Pi by osteoclasts and capillaries of the blood–brain barrier (BBB). Hyperphosphatemia is a risk factor for mineral deposition, the development of diseases such as osteoarthritis, and vascular calcifications (VCs). Na+-independent Pi transporters have been identified and biochemically characterized in vascular smooth muscle cells (VSMCs), chondrocytes, and matrix vesicles, and their involvement in mineral deposition in the extracellular microenvironment has been suggested. According to the growth rate hypothesis, cancer cells require more phosphate than healthy cells due to their rapid growth rates. Recently, it was demonstrated that breast cancer cells (MDA-MB-231) respond to high Pi concentration (2 mM) by decreasing Na+-dependent Pi transport activity concomitant with an increase in Na+-independent (H+-dependent) Pi transport. This Pi H+-dependent transport has a fundamental role in the proliferation and migratory capacity of MDA-MB-231 cells. The purpose of this review is to discuss experimental findings regarding Na+-independent inorganic phosphate transporters and summarize their roles in Pi homeostasis, cancers and other diseases, such as osteoarthritis, and in processes such as VC

Prevention of birth defects in the pre-conception period: knowledge and practice of health care professionals (nurses and doctors) in a city of Southern Brazil

Background: Some congenital defects can be prevented in the pregestational stage. However, many health professionals are not prepared to provide counselling to couples regarding the same. Objective: This study aimed to assess the performance of doctors and nurses from a primary health-care unit in Florianopolis, Brazil, in preventing birth defects in the preconception period based on the recommendations of the Control Center of Disease Prevention. Materials and Methods: This descriptive cross sectional study was performed at a tertiary referral center. In this study, a semi-structured questionnaire was provided to 160 health professionals comprising doctors and nurses who were actively involved in providing primary health care in family health programs. The non-parametric Chi-square (χ2) test was used to analyse the data obtained through multiple choice questions. Results: Our results showed that although 81.9% of health professionals provided health-care assistance based on protocols, and only 46.2% professionals were aware of the presence of the topic in the protocol. Of the recommendations provided by the Control Center of Disease Prevention, the use of folic acid was the most prescribed. However, this prescription was not statistically different between nurses and doctors (P=0.85). Conclusion: This study identified the fragile nature in these professional’s knowledge about the prevention of birth defects in pre-conception period, as evidenced by the inconsistency in their responses

Formulação têxtil contendo flavonoide nanoencapsulado

Universidade Federal do Rio Grande do SulUniversidade Federal de SergipeFarmáciaQuímicaDepositad

Formulação têxtil contendo flavonoide nanoencapsulado

Universidade Federal do Rio Grande do SulUniversidade Federal de SergipeFarmáciaQuímicaDepositad

H+-dependent inorganic phosphate uptake in Trypanosoma brucei is influenced by myo-inositol transporter.

Trypanosoma brucei is an extracellular protozoan parasite that causes human African trypanosomiasis or "sleeping sickness". During the different phases of its life cycle, T. brucei depends on exogenous inorganic phosphate (Pi), but little is known about the transport of Pi in this organism. In the present study, we showed that the transport of 32Pi across the plasma membrane follows Michaelis-Menten kinetics and is modulated by pH variation, with higher activity at acidic pH. Bloodstream forms presented lower Pi transport in comparison to procyclic forms, that displayed an apparent K0.5 = 0.093 ± 0.008 mM. Additionally, FCCP (H+-ionophore), valinomycin (K+-ionophore) and SCH28080 (H+, K+-ATPase inhibitor) inhibited the Pi transport. Gene Tb11.02.3020, previously described to encode the parasite H+:myo-inositol transporter (TbHMIT), was hypothesized to be potentially involved in the H+:Pi cotransport because of its similarity with the Pho84 transporter described in S. cerevisiae and other trypanosomatids. Indeed, the RNAi mediated knockdown remarkably reduced TbHMIT gene expression, compromised cell growth and decreased Pi transport by half. In addition, Pi transport was inhibited when parasites were incubated in the presence of concentrations of myo-inositol that are above 300 μM. However, when expressed in Xenopus laevis oocytes, two-electrode voltage clamp experiments provided direct electrophysiological evidence that the protein encoded by TbHMIT is definitely a myo-inositol transporter that may be only marginally affected by the presence of Pi. These results confirmed the presence of a Pi carrier in T. brucei, similar to the H+-dependent inorganic phosphate system described in S. cerevisiae and other trypanosomatids. This transport system contributes to the acquisition of Pi and may be involved in the growth and survival of procyclic forms. In summary, this work presents the first description of a Pi transport system in T. brucei

Characterization of inorganic phosphate transport in the triple-negative breast cancer cell line, MDA-MB-231

<div><p>Background</p><p>Recent studies demonstrate that interstitial inorganic phosphate is significantly elevated in the breast cancer microenvironment as compared to normal tissue. In addition it has been shown that breast cancer cells express high levels of the NaP_i-IIb carrier (SLC34A2), suggesting that this carrier may play a role in breast cancer progression. However, the biochemical behavior of inorganic phosphate (P_i) transporter in this cancer type remains elusive.</p><p>Methods</p><p>In this work, we characterize the kinetic parameters of Pi transport in the aggressive human breast cancer cell line, MDA-MB-231, and correlated P_i transport with cell migration and adhesion.</p><p>Results</p><p>We determined the influence of sodium concentration, pH, metabolic inhibitors, as well as the affinity for inorganic phosphate in P_i transport. We observed that the inorganic phosphate is dependent on sodium transport (K_0,5 value = 21.98 mM for NaCl). Furthermore, the transport is modulated by different pH values and increasing concentrations of P_i, following the Michaelis-Menten kinetics (K_0,5 = 0.08 mM P_i). PFA, monensin, furosemide and ouabain inhibited P_i transport, cell migration and adhesion.</p><p>Conclusions</p><p>Taken together, these results showed that the uptake of P_i in MDA-MB-231 cells is modulated by sodium and by regulatory mechanisms of intracellular sodium gradient.</p><p>General Significance: Pi transport might be regarded as a potential target for therapy against tumor progression.</p></div

Characterization of inorganic phosphate transport in the triple-negative breast cancer cell line, MDA-MB-231 - Fig 6

<p><b>Effect of inhibitors on cell migration (A) and cell adhesion (B) in MDA-MB-231.</b> Intact cells (5 x 10⁵ cells/mL) were incubated for 1 h at 37°C in a Boyden Chamber Assay™ migration (A) or in a adhesion chamber (B) in the presence or absence (control) of inhibitors indicated in the abscissa: ouabain (1 mM), furosemide (1 mM), Monensin (100 μM) and PFA (5 mM). In the presence of these inhibitors at their respective concentrations, the cells remained viable throughout the experiment. The results are the means ± SE of at least 3 experiments, with different cell suspensions. Asterisks mark significant differences (p≤ 0.05) from control, as determined by One-Way analysis of variance (ANOVA), using Turkey’s multiple comparisons test.</p