Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Signaling by H2S is proposed to occur via persulfidation, a posttranslational modification of cysteine residues (RSH) to persulfides (RSSH). Persulfidation provides a framework for understanding the physiological and pharmacological effects of H2S. Due to the inherent instability of persulfides, their chemistry is understudied. In this review, we discuss the biologically relevant chemistry of H2S and the enzymatic routes for its production and oxidation. We cover the chemical biology of persulfides and the chemical probes for detecting them. We conclude by discussing the roles ascribed to protein persulfidation in cell signaling pathways.

Chemical Biology of H2S Signaling through Persulfidation.

Significance: Hydrogen sulfide (H2S), produced by the desulfuration of cysteine or homocysteine, functions as a signaling molecule in an array of physiological processes including regulation of vascular tone, the cellular stress response, apoptosis, and inflammation. Recent Advances: The low steady-state levels of H2S in mammalian cells have been recently shown to reflect a balance between its synthesis and its clearance. The subversion of enzymes in the cytoplasmic trans-sulfuration pathway for producing H2S from cysteine and/or homocysteine versus producing cysteine from homocysteine, presents an interesting regulatory problem. Critical Issues: It is not known under what conditions the enzymes operate in the canonical trans-sulfuration pathway and how their specificity is switched to catalyze the alternative H2S-producing reactions. Similarly, it is not known if and whether the mitochondrial enzymes, which oxidize sulfide and persulfide (or sulfane sulfur), are regulated to increase or decrease...

Enzymology of H2S biogenesis, decay and signaling.

This article will cover historical and recent aspects of reactions and mechanisms involved in the auxin-induced signalling cascade that terminates in the dramatic elongation growth of cells and plant organs Massive evidence has accumulated that the final target of auxin action is the plasma membrane H+-ATPase, which excretes H+ ions into the cell wall compartment and, in an antiport, takes up K+ ions through an inwardly rectifying K+ channel The auxin-enhanced H+ pumping lowers the cell wall pH, activates pH-sensitive enzymes and proteins within the wall, and initiates cell-wall loosening and extension growth These processes, induced by auxin or by the "super-auxin" fusicoccin, can be blocked instantly and specifically by a voltage inhibition of the H+-ATPase due to removal of K+ ions or the addition of K+-channel blockers Vice versa, H+ pumping and growth are immediately switched on by addition of K+ ions Furthermore, the treatment of segments either with auxin or with fusicoccin (which activates the H+-ATPase irreversibly) or with acid buffers (from outside) causes an identical transformation and degradation pattern of cell wall constituents during cell-wall loosening and growth These and other results described below are in agreement with the acid-growth theory of elongation growth However, objections to this theory are also discussed

Role of the plasma membrane H+-ATPase in auxin-induced elongation growth: historical and new aspects

It has only recently become apparent that the apoplast plays a major role in a diverse range of processes, including intercellular signalling, plant–microbe interactions and both water and nutrient transport. Broadly defined, the apoplast constitutes all compartments beyond the plasmalemma – the interfibrillar and intermicellar space of the cell walls, and the xylem, including its gas- and water-filled intercellular space – extending to the rhizoplane and cuticle of the outer plant surface. The physico-chemical properties of cell walls influence plant mineral nutrition, as nutrients do not simply pass through the apoplast to the plasmalemma but can also be adsorbed or fixed to cell-wall components. Here, current progress in understanding the significance of the apoplast in plant mineral nutrition is reviewed. The contribution of the root apoplast to short-distance transport and nutrient uptakes is examined particularly in relation to Na+ toxicity and Al3+ tolerance. The review extends to long-distance transport and the role of the apoplast as a habitat for microorganisms. In the leaf, the apoplast might have benefits over the vacuole as a site for short-term nutrient storage and solute exchange with the atmosphere.

https://nph.onlinelibrary.wiley.com/doi/epdf/10.1046/j.1469-8137.2001.00034.x

The apoplast and its significance for plant mineral nutrition

Hydrogen sulfide (H2S) has recently been found to play beneficial roles in ameliorating several diseases, including hypertension, atherosclerosis and cardiac/renal ischemia–reperfusion injuries. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), the main enzymes in the transsulfuration pathway, catalyze H2S production in mammalian tissues. However, the distributions and precise roles of these enzymes in the kidney have not yet been identified. The present study examined the localization of both enzymes in the normal kidney and the effect of the H2S donor sodium hydrosulfide (NaHS) in the renal peritubular capillary (PTC) under conditions of diabetic nephropathy, using pancreatic β-cell-specific calmodulin-overexpressing transgenic mice as a model of diabetes. In the normal kidney, we detected expression of both CBS and CSE in the brush border and cytoplasm of the proximal tubules, but not in the glomeruli, distal tubules and vascular endothelial cells of renal PTCs. Administration of NaHS increased PTC diameter and blood flow. We further evaluated whether biosynthesis of H2S was altered in a spontaneous diabetic model that developed renal lesions similar to human diabetic nephropathy. CSE expression was markedly reduced under diabetic conditions, whereas CBS expression was unaffected. Progressive diabetic nephropathy showed vasoconstriction and a loss of blood flow in PTCs that was ameliorated by NaHS treatment. These findings suggest that CSE expression in the proximal tubules may also regulate tubulointerstitial microcirculation via H2S production. H2S may represent a target of treatment to prevent progression of ischemic injury in diabetic nephropathy.

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Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S donor sodium hydrosulfide in diabetic nephropathy

Regardless of their primary causes, progressive renal fibrosis and tubular atrophy are the main predictors of progression to end-stage renal disease. Basigin/CD147 is a multifunctional molecule–it induces matrix metalloproteinases and hyaluronan, for example–and has been implicated in organ fibrosis. However, the relationship between basigin and organ fibrosis has been poorly studied. We investigated basigin's role in renal fibrosis using a unilateral ureteral obstruction model. Basigin-deficient mice (Bsg−/−) demonstrated significantly less fibrosis after surgery than Bsg+/+ mice. Fewer macrophages had infiltrated in Bsg−/− kidneys. Consistent with these in vivo data, primary cultured tubular epithelial cells from Bsg−/− mice produced less matrix metalloproteinase and exhibited less motility on stimulation with transforming growth factor β. Furthermore, Bsg−/− embryonic fibro blasts produced less hyaluronan and α-smooth muscle actin after transforming growth factor β stimulation. Together, these results demonstrate for the first time that basigin is a key regulator of renal fibrosis. Basigin could be a candidate target molecule for the prevention of organ fibrosis.

Basigin/CD147 promotes renal fibrosis after unilateral ureteral obstruction

The role of electrogenic xylem pumps in K+ absorption from the zylem of Vigna unguiculata: the effects of auxin and fusicoccin

A new experimental system was devised for the simultaneous measurement of elongation rate and the activity of the spatially separate electrogenic ion pumps of a hypocotyl segment excised from a seedling of Vigna unguiculata L. Walp. under enforced intra-organ perfusion by artificial solutions. The pathway of the perfusion medium was apoplastic space, including xylem vessels as main routes. The elongation rate of the segment was highly dependent on the perfusion pressure applied. It was possible to increase the growth rate under pressurized perfusion by 10-30 times as much as that without perfusion. Elongation rate was also dependent on respiration under perfusion, being retarded reversibly by anoxia a few minutes after the activities of the electrogenic ion pumps were stopped. Perfusion pressure had a little influence on the membrane potential (Vpx) below a breakdown level (c. 130 kPa). Perfusion of mannitol or sorbitol solution of appropriate concentration reduced the elongation rate reversibly.

A new method in growth‐electrophysiology: Pressurized intra‐organ perfusion

ObjectiveA glycosylated transmembrane protein, CD147, has been implicated in regulating lymphocyte responsiveness and leukocyte recruitment. As lupus nephritis (LN) often follows a relapsing-remitting disease course, accurate understanding of the disease activity would be extremely helpful in improving prognosis. Unfortunately, neither clinical nor serological data can accurately reflect the histological features of LN. The present study investigated whether CD147 can accurately predict pathological features of LN.MethodsPlasma and spot urine samples were collected from 64 patients who underwent renal biopsy between 2008 and 2011. Disease activity for LN tissues was evaluated using the biopsy activity index, and compared to levels of biomarkers including CD147.ResultsIn LN tissues, CD147 induction was striking in injured glomeruli and infiltrating inflammatory cells, but not in damaged tubules representing atrophy. Plasma CD147 levels accurately reflected the histological disease activity. However, predic...

Hiroshi Kojima

Papers

Distribution of hydrogen sulfide (H2S)-producing enzymes and the roles of the H2S donor sodium hydrosulfide in diabetic nephropathy

Basigin/CD147 promotes renal fibrosis after unilateral ureteral obstruction

The role of electrogenic xylem pumps in K+ absorption from the zylem of Vigna unguiculata: the effects of auxin and fusicoccin

A new method in growth‐electrophysiology: Pressurized intra‐organ perfusion

Plasma CD147 reflects histological features in patients with lupus nephritis.