Cholesteryl butyrate solid lipid nanoparticles (chol-but SLN) have been proposed as a pro-drug to deliver butyric acid. We compared the effects on cell growth, cell-cycle distribution and c-myc ...expression of chol-but SLN and sodium butyrate (Na-but) in the human leukemic cell lines Jurkat, U937 and HL-60. In all the cell lines 0.5 and 1.0 mM chol-but SLN provoked a complete block of cell growth. Cell-cycle analysis demonstrated in Jurkat cells that 0.25 mM chol-but SLN caused a pronounced increase of G2/M cells and a decrease of G0/G1 cells, whereas in U937 and HL-60 cells chol-but SLN led to a dose-dependent increase of G0/G1 cells, with a decrease of G2/M cells. In Jurkat and HL-60 cells 0.5 mM chol-but SLN induced a significant increase of sub-G0/G1 apoptotic cells. Cell growth and cell-cycle distribution were unaffected by the same concentrations of Na-but. A concentration of 0.25 mM chol-but SLN was able to cause a rapid and transient down-regulation of c-myc expression in all the cell lines, whereas 1 mM Na-but caused a slight reduction of c-myc expression only in U937 cells. The results show how chol-but SLN affects the proliferation pattern of both myeloid and lymphoid cells to an extent greater than the natural butyrate.
4-Hydroxynonenal (HNE) is a highly reactive aldehyde, produced by cellular lipid peroxidation, able to inhibit proliferation and to induce differentiation in MEL cells at concentrations similar to ...those detected in several normal tissues. Inducer-mediated differentiation of murine erythroleukemia (MEL) cells is a multiple step process characterized by modulation of several genes as well as by a transient increase in the amount of membrane-associated protein kinase C (PKC) activity. Here we demonstrate that a rapid translocation of PKC activity from cytosol to the membranes occurs during the differentiation induced by HNE. When PKC is completely translocated by phorbol-12-myristate-13-acetate (TPA), the degree of HNE-induced MEL cells differentiation is highly decreased. However, if TPA is washed out from the culture medium before the exposition to the aldehyde, HNE gradually resumes its differentiative ability. The incubation of cells with a selective inhibitor of PKC activity, bisindolylmaleimide GF 109203X, partially prevents the HNE-induced differentiation in MEL cells. In conclusion, our results demonstrate that HNE-induced MEL cell differentiation is preceded by a rapid translocation of PKC activity, and that the inhibition of this phenomenon prevents the onset of terminal differentiation.
4-Hydroxynonenal (HNE) is a highly reactive aldehyde produced by lipid peroxidation of cellular membranes that inhibits growth and induces differentiation in HL-60 cells. Its mechanisms of action ...were investigated by analyzing the cell cycle distribution and the appearance of differentiated phenotypes in HL-60 cells. Data obtained by exposing cells to DMSO for 7.5 h (same time as for HNE treatment) or for the whole length of the experiments (5 d) were used for comparison. HNE induced a marked increase in the proportion of G0/G1 cells after 1 and 2 d. The brief DMSO treatment did not affect the distribution, whereas continuous exposure led to a progressive accumulation of cells in G0/G1 (maximal at day 5). The proportion of phagocytic cells gradually increased in HNE-treated and DMSO long-exposed cultures from day 2 and peaked at day 5 (35 and 63%, respectively), whereas the effect of the brief DMSO treatment was negligible. The expression of CDllb and CD67 increased in cells treated with HNE or continuously exposed to DMSO, whereas CD36 was expressed at low levels on both treatments. These results indicate that the pathway of the granulocytic differentiation induced by HNE in HL-60 cells differs from that of DMSO: with HNE, growth inhibition precedes the onset of differentiation, whereas in DMSO-treated cells the two processes are chronologically associated.
4-Hydroxynonenal, an aldehyde produced from lipid peroxidation of cellular membranes, inhibits growth and induces differentiation of HL-60 human leukemic cell line. Since it is highly unstable in the ...culture medium, its effectiveness is increased when added repeatedly to the cell suspension. We have previously demonstrated that HNE inhibits c-myc but not N-ras expression in HL-60 cells. Here we investigate its effect on the expression of c-myb and c-fos, two early genes involved in the induction of myeloid and monocytic differentiation. Moreover, since c-fos is directly correlated with the intracellular level of cAMP, we also analysed the cAMP concentration after aldehyde treatment. HNE significantly inhibits c-myb expression during and after repeated treatments. A single administration of 1 μM HNE decreases c-myb mRNA at 1 hour whereas 10 μM HNE inhibits c-myb expression from 3 to 6 hours after treatment, and then the expression returns to the control level. By contrast, c-fos expression and intracellular cAMP concentration do not show any significant change after HNE treatments.
4-Hydroxynonenal (HNE) is one of the major end products of lipid peroxidation. Here we show that the exposure of murine erythroleukemia (MEL) cells to 1 μM HNE, for 10.5 h over 2 days, induces a ...differentiation comparable with that observed in cells exposed to DMSO for the whole experiment (7 days). The exposure of MEL cells for the same length of time demonstrates a higher degree of differentiation in HNE-treated than in DMSO-treated MEL cells. The protooncogene c-myc is down-modulated early, in HNE-induced MEL cells as well as in DMSO-treated cells. However, ornithine decarboxylase gene expression first increases and then decreases, during the lowering of the proliferation rate. These findings indicate that HNE, at a concentration physiologically found in many normal tissues and in the plasma, induces MEL cell differentiation by modulation of specific gene expression.
Although recent studies have revealed that heart cells are generated in adult mammals, the frequency of generation and the source of new heart cells are not yet known. Some studies suggest a high ...rate of stem cell activity with differentiation of progenitors to cardiomyocytes. Other studies suggest that new cardiomyocytes are born at a very low rate, and that they may be derived from the division of pre-existing cardiomyocytes. Here we show, by combining two different pulse-chase approaches--genetic fate-mapping with stable isotope labelling, and multi-isotope imaging mass spectrometry--that the genesis of cardiomyocytes occurs at a low rate by the division of pre-existing cardiomyocytes during normal ageing, a process that increases adjacent to areas of myocardial injury. We found that cell cycle activity during normal ageing and after injury led to polyploidy and multinucleation, but also to new diploid, mononucleate cardiomyocytes. These data reveal pre-existing cardiomyocytes as the dominant source of cardiomyocyte replacement in normal mammalian myocardial homeostasis as well as after myocardial injury.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Literature devoted to party organizations rarely relies on Organization Theory. With the exception of the fundamental contribution by Panebianco, which dates back to 1982, limited efforts have been ...made towards a mutual contamination between the study of party organizational development and the vast body of theories, approaches and analytical frameworks that crowd Organization Theory. Moreover, while Organization Theory has recently paid attention to the study of political parties, party scholars are still committed to accumulating empirical knowledge or, at best, elaborating ideal-typical models. The aim of this contribution is to favour a cross-fertilization between these two literatures, by building on the premises of organizational institutionalism and on the organizations as multi-dimensional rational open systems perspective. Despite our effort is primarily conceptual, our arguments are conceived to be properly translated into empirical observations.
Davide Gangale Risoleo, Ippolita Raimondo (eds), Landscape: una sintesi di elementi diacronici. Metodologie a confronto per l’analisi del territorio, BAR International Series 3047, Oxford, 2021 | ...Book review
ABSTRACT
High‐resolution tract tracing and stereology were used to study the terminal organization of the corticospinal projection (CSP) from the ventral (v) and dorsal (d) regions of the lateral ...premotor cortex (LPMC) to spinal levels C5–T1. The LPMCv CSP originated from the postarcuate sulcus region, was bilateral, sparse, and primarily targeted the dorsolateral and ventromedial sectors of contralateral lamina VII. The convexity/lateral part of LPMCv did not project below C2. Thus, very little LPMCv corticospinal output reaches the cervical enlargement. In contrast, the LPMCd CSP was 5× more prominent in terminal density. Bilateral terminal labeling occurred in the medial sectors of lamina VII and adjacent lamina VIII, where propriospinal neurons with long‐range bilateral axon projections reside. Notably, lamina VIII also harbors axial motoneurons. Contralateral labeling occurred in the lateral sectors of lamina VII and the dorsomedial quadrant of lamina IX, noted for harboring proximal upper limb flexor motoneurons. Segmentally, the CSP to contralateral laminae VII and IX preferentially innervated C5–C7, which supplies shoulder, elbow, and wrist musculature. In contrast, terminations in axial‐related lamina VIII were distributed bilaterally throughout all cervical enlargement levels, including C8 and T1. These findings demonstrate the LPMCd CSP is structured to influence axial and proximal upper limb movements, supporting Kuypers conceptual view of the LPMCd CSP being a major component of the medial motor control system. Thus, distal upper extremity control influenced by LPMC, including grasping and manipulation, must occur through indirect neural network connections such as corticocortical, subcortical, or intrinsic spinal circuits.
Using high‐resolution tract tracing, the authors demonstrate the dorsal lateral premotor cortex (LPMCd) gives rise to a prominent bilateral corticospinal projection (CSP) involving the ventromedial (red) and lateral (blue) gray matter regions. In contrast a weaker bilateral CSP arose from the peri‐arcuate region of ventral lateral premotor cortex (LPMCv).
PDF
