Experimental colitis is associated with transcriptional inhibition of Na+/Ca2+ exchanger isoform 1 (NCX1) expression by interferon γ in the renal distal convoluted tubules.

NCX1 is a Na(+)/Ca(2+) exchanger, which is believed to provide a key route for basolateral Ca(2+) efflux in the renal epithelia, thus contributing to renal Ca(2+) reabsorption. Altered mineral homeostasis, including intestinal and renal Ca(2+) transport may represent a significant component of the pathophysiology of the bone mineral density loss associated with Inflammatory Bowel Diseases (IBD). The objective of our research was to investigate the effects of TNBS and DSS colitis and related inflammatory mediators on renal Ncx1 expression. Colitis was associated with decreased renal Ncx1 expression, as examined by real-time RT-PCR, Western blotting, and immunofluorescence. In mIMCD3 cells, IFNγ significantly reduced Ncx1 mRNA and protein expression. Similar effects were observed in cells transiently transfected with a reporter construct bearing the promoter region of the kidney-specific Ncx1 gene. This inhibitory effect of IFNγ is mediated by STAT1 recruitment to the proximal promoter region of Ncx1. Further in vivo study with Stat1(-/-) mice confirmed that STAT1 is indeed required for the IFNγ mediated Ncx1 gene regulation. These results strongly support the hypothesis that impaired renal Ca(2+) handling occurs in experimental colitis. Negative regulation of NCX1- mediated renal Ca(2+) absorption by IFNγ may significantly contribute to the altered Ca(2+) homeostasis in IBD patients and to IBD-associated loss of bone mineral density.

Intrusive growth of initials does not affect cambial circumference in Robinia pseudoacacia.

This study aimed to test the hypothesis whether intrusive growth of initial cells is related to the increase in circumference of Robinia pseudoacacia vascular cambium-both qualitatively and quantitatively. The mode of intrusive growth of cambial initial cells was also studied. Samples collected from tree trunks were examined using series of semi-thin transverse sections. Anatomical reconstructions of radial and tangential planes of analysed fragments of cambial tissue were made. Observations and measurements have shown that the intrusive growth of R. pseudoacacia initial cells does not contribute to an increase in tangential dimension of observed tissue fragments where cell rearrangement occurs. Moreover, initially separated tangential walls of cells (between which cambial initial cell elongates intrusively) are transformed into obliquely oriented walls. These results stand in accordance with a statement that only symplastic growth of initials, not intrusive growth, is responsible for the increase in circumference in all woody plants with the continuous cambial cylinder. Moreover, we managed to capture the moment of transition of initial status from one cell to another for the first time. This phenomenon may be explained on the basis of the system of mechanical stresses operating not only in the secondary meristematic tissue but also in a whole plant organism.

What do we know about growth of vessel elements of secondary xylem in woody plants?

Despite extensive knowledge about vessel element growth and the determination of the axial course of vessels, these processes are still not fully understood. They are usually explained as resulting primarily from hormonal regulation in stems. This review focuses on an increasingly discussed aspect - mechanical conditions in the vascular cambium. Mechanical conditions in cambial tissue are important for the growth of vessel elements, as well as other cambial derivatives. In relation to the type of stress acting on cambial cells (compressive versus tensile stress) we: (i) discuss the shape of the enlarging vessel elements observed in anatomical sections; (ii) present hypotheses regarding the location of intrusive growth of vessel elements and cambial initials; (iii) explain the relationship between the growth of vessel elements and fibres; and (iv) consider the effect of mechanical stress in determining the course of a vessel. We also highlight the relationship between mechanical stress and transport of the most extensively studied plant hormone - auxin. We conclude that the integration of a biomechanical factor with the commonly acknowledged hormonal regulation could significantly enhance the analysis of the formation of vessel elements as well as entire vessels, which transport water and minerals in numerous plant species.

Readjustments of cambial initials in Wisteria floribunda (Willd.) DC. for development of storeyed structure.

• This study has elucidated the mechanism of development of the storeyed cambial structure of Wisteria floribunda, a species characterised by very quick and early establishment of storeyed structure from a nonstoreyed procambium in close vicinity of the pith. • Rearrangement of the cambial cells was studied in serial tangential longitudinal sections of axial wood parenchyma. • The mechanism of cell rearrangement was found to involve not only the occurrence of anticlinal cell divisions, but also a concomitant intrusive growth of the ends of cambial cells of one cell packet along the tangential walls of cells of the neighbouring packet. During the process, the fusiform initials changed their position along the stem axis and became arranged in regular storeys. New positions of cells were thus achieved through first the vertical intrusion of cell ends between the tangential walls of neighbouring cells, and second the unequal periclinal cell divisions. • The concept that radial longitudinal divisions of the fusiform initials are the main cause of the formation of storeyed structure of the cambium has been critically examined.

pTyr421 cortactin is overexpressed in colon cancer and is dephosphorylated by curcumin: involvement of non-receptor type 1 protein tyrosine phosphatase (PTPN1).

Cortactin (CTTN), first identified as a major substrate of the Src tyrosine kinase, actively participates in branching F-actin assembly and in cell motility and invasion. CTTN gene is amplified and its protein is overexpressed in several types of cancer. The phosphorylated form of cortactin (pTyr(421)) is required for cancer cell motility and invasion. In this study, we demonstrate that a majority of the tested primary colorectal tumor specimens show greatly enhanced expression of pTyr(421)-CTTN, but no change at the mRNA level as compared to healthy subjects, thus suggesting post-translational activation rather than gene amplification in these tumors. Curcumin (diferulolylmethane), a natural compound with promising chemopreventive and chemosensitizing effects, reduced the indirect association of cortactin with the plasma membrane protein fraction in colon adenocarcinoma cells as measured by surface biotinylation, mass spectrometry, and Western blotting. Curcumin significantly decreased the pTyr(421)-CTTN in HCT116 cells and SW480 cells, but was ineffective in HT-29 cells. Curcumin physically interacted with PTPN1 tyrosine phosphatases to increase its activity and lead to dephosphorylation of pTyr(421)-CTTN. PTPN1 inhibition eliminated the effects of curcumin on pTyr(421)-CTTN. Transduction with adenovirally-encoded CTTN increased migration of HCT116, SW480, and HT-29. Curcumin decreased migration of HCT116 and SW480 cells which highly express PTPN1, but not of HT-29 cells with significantly reduced endogenous expression of PTPN1. Curcumin significantly reduced the physical interaction of CTTN and pTyr(421)-CTTN with p120 catenin (CTNND1). Collectively, these data suggest that curcumin is an activator of PTPN1 and can reduce cell motility in colon cancer via dephosphorylation of pTyr(421)-CTTN which could be exploited for novel therapeutic approaches in colon cancer therapy based on tumor pTyr(421)-CTTN expression.