Alkalinization of sperm cytosol is essential for plasma membrane hyperpolarization, hyperactivation of motility, and acrosomal exocytosis during sperm capacitation in mammals. The plasma membrane of sperm cells contains different ion channels implicated in the increase of internal pH (pHi) by favoring either bicarbonate entrance or proton efflux. Bicarbonate transporters belong to the solute carrier families 4 (SLC4) and 26 (SLC26) and are currently grouped into Na+/HCO3- transporters and Cl-/HCO3- exchangers. Na+/HCO3- transporters are reported to be essential for the initial and fast entrance of HCO3- that triggers sperm capacitation, whereas Cl-/HCO3- exchangers are responsible for the sustained HCO3- entrance which orchestrates the sequence of changes associated with sperm capacitation. Proton efflux is required for the fast alkalinization of capacitated sperm cells and the activation of pH-dependent proteins; according to the species, this transport can be mediated by Na+/H+ exchangers (NHE) belonging to the SLC9 family and/or voltage-gated proton channels (HVCN1). Herein, we discuss the involvement of each of these channels in sperm capacitation and the acrosome reaction.

In this review, we discuss the role of adrenoceptors in the regulation of the rheological functions of erythrocytes. β-adrenoceptors play an important role in the regulation of erythrocytes functions and metabolism. They participate in the modification of transport membrane proteins (Na+/K+-ATPase, Ca+2-ATPase, Na+/K+/2Cl-cotransporter, Na+/H+-antiporter, CAT-1, Ca2+-dependent K+ channels (Gard channels), the activity of adenylate cyclase and cAMP, AMP-dependent activation of the L-arginine/NOS system and erythrocyte NOS) and by this way modulate the cells volume, rheological properties (deformability, aggregability), intensity of NO synthesis and ATP reliase. These properties of erythrocytes determine, that, in addition to the transport of gases, they play the oxygen sensors role and can participate in the mechanisms of vasorelaxation and maintenance of a normal level of microcirculation.

Na+/H+ exchange regulatory factor 1 (NHERF1), a member of a PDZ scaffolding protein family, was first identified as an organizer of membrane-bound protein complexes composed of hormone receptors, signal transduction pathways, and electrolyte and mineral transporters and channels. NHERF1 is involved in the regulation of Na+/H+ exchanger 3, Na+-dependent phosphate transporter 2a, and Na+-K+-ATPase through its ability to scaffold these transporters to the plasma membrane, allowing regulation of these protein complexes with their associated hormone receptors. Recently, NHERF1 has received increased interest in its involvement in a variety of functions, including cell structure and trafficking, tumorigenesis and tumor behavior, inflammatory responses, and tissue injury. In this review, we highlight the evidence for the expansive role of NHERF1 in cell biology and speculate on the implications for renal physiology and pathophysiology.

Christianson syndrome (OMIM 300243), caused by mutations in the X-linked SLC9A6 gene, is characterized by severe global developmental delay and intellectual disability, developmental regression, epilepsy, microcephaly and impaired ocular movements. It shares many common features with Angelman syndrome. Carrier females have been described as having learning difficulties with mild to moderate intellectual disability, behavioural issues and psychiatric illnesses. There is little literature on the carrier female phenotype of Christianson syndrome. We describe a large extended family with three affected males, four carrier females, one presumed carrier female and one obligate carrier female with a c.190G>T, p.E64X mutation known to cause a premature stop codon in SLC9A6. We characterize and expand the clinical phenotype of female SLC9A6 mutation carriers by comparing our described family with female carriers previously discussed in the literature. In particular, we highlight the neurodevelopmental and psychiatric phenotypes observed in our family and previous reports.

BACKGROUND: Salt stress has become a major threat to plant growth and productivity. Arbuscular mycorrhizal fungi colonize plant root systems and modulate plant growth in various ways.
METHODS: This review addresses the significance of arbuscular mycorrhiza in alleviation of salt stress and their beneficial effects on plant growth and productivity. It also focuses on recent progress in unravelling biochemical, physiological and molecular mechanisms in mycorrhizal plants to alleviate salt stress.
CONCLUSIONS: The role of arbuscular mycorrhizal fungi in alleviating salt stress is well documented. This paper reviews the mechanisms arbuscular mycorrhizal fungi employ to enhance the salt tolerance of host plants such as enhanced nutrient acquisition (P, N, Mg and Ca), maintenance of the K(+) : Na(+) ratio, biochemical changes (accumulation of proline, betaines, polyamines, carbohydrates and antioxidants), physiological changes (photosynthetic efficiency, relative permeability, water status, abscissic acid accumulation, nodulation and nitrogen fixation), molecular changes (the expression of genes: PIP, Na(+)/H(+) antiporters, Lsnced, Lslea and LsP5CS) and ultra-structural changes. Theis review identifies certain lesser explored areas such as molecular and ultra-structural changes where further research is needed for better understanding of symbiosis with reference to salt stress for optimum usage of this technology in the field on a large scale. This review paper gives useful benchmark information for the development and prioritization of future research programmes.

Thiazolidinediones (TZD) such as pioglitazone and rosiglitazone are proxisome proliferator-activated receptor gamma (PPARg) agonists and are widely used clinically to treat type 2 diabetes mellitus. Fluid retention still poses a significant limitation to its use. The primary renal process underlying TZD-associated oedema is reduced urinary sodium and water excretion. Experimental evidence suggests that this is mainly related to the effects of PPARg agonists on the distal nephron and collecting duct. We have recently shown that PPARg agonists upregulate sodium and water transport channels in human proximal tubule cells and that Sgk-1 is involved. In this review, we focus on the importance of the proximal tubular cells in TZD-mediated sodium and water uptake.

The principal therapy in patients with myocardial infarction to limit infarct size is myocardial reperfusion by mechanical or pharmacological intervention. Reperfusion has been proposed to cause myocardial injury beyond that caused by the preceding ischaemia, termed \"reperfusion injury\" (RI). While the precise mechanism of RI is still incompletely understood, a large number of clinical studies have been performed over the past decade targeting some of the postulated mechanisms of RI. These clinical studies were based on experimental data demonstrating significant myocardial salvage. Nevertheless, clinical benefits were absent or very limited. The purpose of this review is to provide an overview of the various strategies that inhibit RI and to discuss potential mechanisms that may contribute to the discrepancy between the promising pre-clinical data and the rather disappointing results obtained from prospective clinical trials. There are numerous differences between the experimental models and clinical studies, including the fact that experimental studies typically use abrupt occlusion and reperfusion protocols in animals with previously healthy myocardium that apparently do not predict the therapeutic efficacy of novel cardioprotective agents in a clinical setting with pre-existing progressive coronary disease, intermittent coronary occlusion, and relatively late reperfusion. However, discrepancies also exist between experimental studies. Future experimental studies of reperfusion injury should use models that mimic the clinical situation more closely. Furthermore, future large clinical trials should only be performed in cases where the drug under investigation proved to reduce RI in a series of well-designed (possibly multicenter) experimental studies and in clinical trials with predefined subgroups.

暂无摘要。

BACKGROUND: The Guard During Ischemia Against Necrosis (GUARDIAN) trial was designed to determine whether cariporide, a selective sodium-hydrogen exchanger inhibitor, reduces the combined incidence of all-cause mortality and myocardial infarction (MI) in patients at risk of myocardial necrosis and to assess the safety and tolerability of this drug.
RESULTS: The study population consisted of 11,590 patients who were hospitalized for an acute coronary syndrome or were undergoing high-risk percutaneous coronary intervention or coronary artery bypass grafting (CABG). Patients were enrolled and randomized to one of three doses of cariporide (20, 80, or 120 mg), or placebo, administered as a 60-minute infusion every 8 hours for two to seven days. At day 36, patients treated with cariporide 120 mg demonstrated a 10% risk reduction in death or MI compared with placebo (p = 0.12). At this dose, patients undergoing CABG experienced a 25% risk reduction in death or MI (p = 0.03), which was sustained through six months (p = 0.033). The improvement resulted primarily from a 32% risk reduction in nonfatal MI (p = 0.007). Cariporide was well tolerated; most adverse events were mild and transient. Data from the GUARDIAN trial indicate that myocardial muscle creatine kinase isoenzyme (CK-MB) values of >10 times the upper limit of normal during the initial 48 hours after CABG are associated with significantly increased six-month mortality (p < 0.001); the six-month mortality risk is similar to that observed in acute coronary syndrome patients, even after adjustment for baseline variables known to impact long-term prognosis.
CONCLUSIONS: Although the results of the GUARDIAN trial failed to demonstrate overall clinical benefit, cariporide 120 mg reduced the rate of death and MI in patients undergoing CABG. Cariporide may provide a cardioprotective benefit in CABG patients at high-risk of myocardial necrosis.

This review article considers the purposes and mechanisms of regulation of placental transfer in general terms and then illustrates some key points with reference to the Na(+)/H(+) exchanger (NHE), a transport protein found in the syncytiotrophoblast. NHE probably has a role in the homeostasis of syncytiotrophoblast intracellular pH and may also be involved in syncytiotrophoblast cell volume regulation as well as H(+) loss from and Na(+) transfer to the fetus. The activity and expression of NHE in the microvillous plasma membrane of the syncytiotrophoblast is reduced in placentas from preterm, growth restricted babies as compared to their gestationally matched normally grown counterparts. There are differential effects of gestation in normal pregnancy on NHE mRNA, NHE protein and NHE activity. There is also evidence of acute modulation of NHE activity. Regulation of NHE in syncytiotrophoblast is therefore complex with control at transcription, post transcription and post translational loci.