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S Pizzimenti

Publications and source records attributed to S Pizzimenti.

10 recordsLinked to original sources
PubMed2002

Peripheral inflammatory response in Alzheimer's disease and multiinfarct dementia.

Whether peripheral inflammatory molecules can be considered markers of dementia is still an open issue. We have investigated the presence of circulating cytokines and the ability of blood cells to release them in response to an inflammatory stimulus in patients with different types of dementia and in age-matched controls. A significant increase in circulating interleukin-1beta in moderate Alzheimer and in multiinfarct (145 and 224 times control concentration, respectively) dementia and in circulating tumor necrosis factor-alpha concentration in multiinfarct dementia patient group (156%) were found. Tumor necrosis factor-alpha and interleukin-6 released from blood cells after exposure to lipopolysaccharide were significantly reduced in moderate Alzheimer (60%, both cytokines) and multiinfarct patients (71 and 50%, respectively), while interleukin-10 was decreased only in multiinfarct patients (61%). The results show that patients with Alzheimer disease or multiinfarct dementia have an upregulation of circulating cytokines and a downregulation of cytokines released by blood cells.

Alzheimer Disease↗
PubMed2001

Growth inhibition and differentiation induction in murine erythroleukemia cells by 4-hydroxynonenal.

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 microM 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.

Aldehydes↗
PubMed2000

4-Hydroxynonenal-induced MEL cell differentiation involves PKC activity translocation.

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.

Aldehydes↗
PubMed2000

Effect of bioactive aldehydes on cell proliferation and c-myc expression in HL-60 human leukemic cells.

Lipid peroxidation produces several toxic carbonyls, including biologically active aldehydes. In previous studies, we demonstrated that 4-hydroxynonenal (HNE), one of the major products of lipoperoxidation, inhibited growth and c-myc expression in K562 and HL-60 human leukemic cells. In this study, we compared the HNE effects with those of 4-hydroxyoctenal (HOE), 4-hydroxyundecenal (HUE; different lengths of the lipophilic tail), and the analogous aldehydes 2-trans-nonanal (lacking the OH group) and nonenal (lacking the OH group and the trans CC double bond), on HL-60 cell proliferation and c-myc expression. HUE and HOE inhibited growth and c-myc expression in a dose-dependent fashion, with an effectiveness comparable with that of HNE, whereas 2-nonenal and nonanal did not affect these parameters. Our results showed that different aldehydes produced from lipid peroxidation may contribute to growth inhibition by c-myc downregulation and that the molecular features involved seem to be the hydroxy group and the trans CC double bond.

Aldehydes↗
PubMed1999

Inhibition of D1, D2, and A-cyclin expression in HL-60 cells by the lipid peroxydation product 4-hydroxynonenal.

4-Hydroxynonenal (HNE), a product of lipid peroxidation, is an highly reactive aldehyde that, at concentration similar to those found in normal cells, blocks proliferation and induces a granulocytic-like differentiation in HL-60 cells. These effects are accompained by a marked increase in the proportion G0/G1 cells. The mechanisms of HNE action were investigated by analyzing the expression of the cyclins and cyclin-dependent protein kinases (CDKs), controlling the cell cycle progression. Data obtained by exposing cells to dimethyl sulfoxide (DMSO) were used for comparison. 4-Hydroxynonenal downregulated both mRNA and protein contents of cyclins D1, D2, and A until 24 h from the treatments, whereas DMSO inhibited cyclin D1 and D2 expression until the end of experiment (2 days) and induces an increase of cyclin A until 1 day. Cyclins B and E, and protein kinase CDK2 and CDK4 expressions were not affected by HNE, whereas DMSO induced an increase of cyclin E, B, and CDK2 from 8 h to 1 day. These data are in agreement with previous results indicating a different time-course of accumulation in G0/G1 phases of cells treated with HNE and DMSO and suggest that the HNE inhibitory effect on proliferation and cell cycle progression may depend by the downregulation of D1, D2, and A cyclin expression.

Aldehydes↗
PubMed1996

4-hydroxynonenal specifically inhibits c-myb but does not affect c-fos expressions in HL-60 cells.

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 microM HNE decreases c-myb mRNA at 1 hour whereas 10 microM 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.

Aldehydes↗
PubMed1996

Enzymatic pattern of aldehyde metabolism during HL-60 cell differentiation.

A number of metabolic changes, including modification of different enzyme activities, are linked to the acquisition of differentiated phenotype in HL-60 cells. Enzymes metabolizing aldehydes contribute to maintaining the intracellular steady-state concentration of aldehydes derived from lipid peroxidation. 4-Hydroxynonenal is one of the most important aldehydes produced by this process, and it is able to inhibit proliferation and induce differentiation of HL-60 human leukemic cells. We have now demonstrated that, after induction of HL-60 cell differentiation by 4-hydroxynonenal or DMSO, glutathione transferase activity increases in parallel to the degree of differentiation induction. Moreover, in 4-hydroxynonenal- or DMSO-treated cells, the concentration of reduced glutathione decreases five days after treatment. The rise of glutathione transferase activity, as well as the decrease of reduced glutathione, are possibly linked to the increase of detoxification capability of differentiated cells.

Alcohol Dehydrogenase↗
PubMed1996

Effect of 4-Hydroxynonenal on cell cycle progression and expression of differentiation-associated antigens in HL-60 cells.

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 CD11b 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.

Aldehydes↗
PubMed1994

Inhibition of c-myc expression induced by 4-hydroxynonenal, a product of lipid peroxidation, in the HL-60 human leukemic cell line.

4-Hydroxynonenal is a highly reactive aldehyde, produced by cellular lipid peroxidation, able to inhibit cell proliferation "in vitro" and "in vivo". Its concentration in non proliferating cells ranges up to 1 microM, whereas in the highly undifferentiated tumour cells, it is very low or undetectable. We have now demonstrated that micromolar concentrations of 4-hydroxynonenal inhibit c-myc but not N-ras expression in HL-60 human leukemic cells. This inhibitory effect is observed after an incubation of 1 hour with both 1 and 10 microM aldehyde. Moreover, we report that down-regulation of c-myc expression increases when repeated additions of 1 microM 4-hydroxynonenal are performed, to maintain the cells in presence of aldehyde for 7.5 hours. These results indicate that not only the concentration but also the length of exposure to the aldehyde is important in determining the extent of the c-myc expression inhibition and suggest a role of lipid peroxidation products in the control of gene expression.

Aldehydes↗