Regulation of the expression of lactate dehydrogenase isozymes in human lymphocytes

Patrik, Wollberg; Bd, Nelson

doi:10.1007/bf02454193

Cited by 10 publications

(4 citation statements)

References 23 publications

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“…The raft analysis revealed that Nef is associated with recruitment of the RNA binding protein hnRNP E1 that localizes to spreading initiation centers present in the early stages of cell spreading prior to the formation of focal adhesions (de Hoog et al, 2004). Signaling proteins recruited to rafts in the presence of Nef include lactate dehydrogenase-A isoform that is preferentially expressed in activated lymphocytes (Wollberg and Nelson, 1992). Finally, Nefpositive rafts lack a known negative regulator of signaling, 14-3-33.…”

Section: Resultsmentioning

confidence: 98%

Nef-Mediated Lipid Raft Exclusion of UbcH7 Inhibits Cbl Activity in T Cells to Positively Regulate Signaling

et al. 2005

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Lentiviral Nef increases T cell signaling activity, but the molecular nature of the stimulus involved is incompletely described. We explored CD4 T cell lipid raft composition in the presence and absence of Nef. Here, the E2 ubiquitin-conjugating enzyme UbcH7, which acts in conjunction with c-Cbl, is absent from lipid rafts. This Nef-mediated exclusion is associated with failure of ubiquitination of activated Vav. In the presence of Nef, lipid raft Cdc42 is activated and forms a ternary complex between the c-Cbl-interacting protein p85Cool-1/betaPix and c-Cbl, displacing UbcH7 from rafts. Suppression of p85Cool-1/betaPix expression restores UbcH7 raft localization and Vav ubiquitination and diminishes Cdc42 activity. Moreover, p85Cool-1/betaPix knockdown attenuates HIV replication. Thresholds for activation of signaling involve the intricate balance of positive and negative regulators. Here we provide evidence for Nef disruption of a negative regulator of T cell signaling in promoting HIV replication.

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Section: Resultsmentioning

confidence: 98%

Nef-Mediated Lipid Raft Exclusion of UbcH7 Inhibits Cbl Activity in T Cells to Positively Regulate Signaling

et al. 2005

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“…The activation of lymphocytes is accompanied by an increase in the speci®c activities of several glycolytic enzymes. Moreover, the increase in intracellular LDH activity has been shown to be a programmed event in the lymphoid activation cascade (11,21). This is based on previous in vitro studies showing that mitogens, PHA and Con A (10, 11), or activators, such as phorbol ester (21,22), in association with activation of different intracellular pathways, induce marked LDH elevation (23).…”

Section: Discussionmentioning

confidence: 98%

“…In this sense, aside from very useful measurements of serum LDH level, the intracellular characteristics of this enzyme and its isotype pro®le are very sensitive indicators of the cellular metabolic state (9), aerobic or anaerobic direction of glycolysis (10), activation status (11), malignant transformation (12), as well as membrane damage (13,14).…”

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confidence: 99%

Different alterations in lactate dehydrogenase activity and profile of peripheral blood mononuclear cells in Hodgkin's and non‐Hodgkin's lymphomas

Jurišić

Konjević

Banićević³

et al. 2000

European J of Haematology

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The enzyme lactate dehydrogenase (LDH) activity of peripheral blood mononuclear cells (PBMC), LDH isotype H and M pattern and PBMC spontaneous LDH release activity were examined in 55 non-Hodgkin's lymphoma (NHL) patients, 46 Hodgkin's disease (HD) patients and 47 controls. The intracellular LDH and M isotype activity of PBMC, their spontaneous LDH release activity significantly increase (p < 0.01) in NHL with progressing histological grade of malignancy. Contrary to this, all classical HD patients have a significant elevation (p < 0.05) of each of these parameters. Furthermore, unlike HD, in NHL clinical stage is associated with significant (p < 0.05) increase in the level of spontaneous LDH release activity in each histological form. It is also shown that spontaneous LDH release activity of PBMC for HD and NHL patients demonstrates significant positive correlation (p < 0.005) with serum LDH level, although elevation of spontaneous LDH release precedes serum LDH increase in both diseases. The results obtained regarding alterations in intracellular, isotype and spontaneously released LDH activity of circulating PBMC show that these parameters are dependent, in NHL patients, on the grade of malignancy and tumor burden, while they are persistently present in HD patients.

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“…Evaluation of LDH owing to its very well-defined structural and kinetic characteristics gives valuable data considering cellar metabolic status. In that sense, analyses of the intracellular ratio of LDH isotypes, H to M, indicate the direction of pyruvate-lactate conversion and give data whether glycolysis is of aerobic or anaerobic type [57,58]. In this sense, aside from very useful measurements of serum LDH level, we showed that the intracellular PBL characteristics of this enzyme and its isotype profile are very sensitive indicators of the cellular metabolic state, aerobic or anaerobic direction of glycolysis, activation status, malignant transformation, as well as membrane damage.…”

Section: Nk Cell Dysfunction and Its Association With Ldh Release Fro...mentioning

confidence: 99%

Investigation of NK cell function and their modulation in different malignancies

et al. 2012

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NK cells have become a subject of investigation not only in the field of tumor immunology and infectious diseases, but also within all aspects of immunology, such as transplantation, autoimmunity, and hypersensitivity. Our early studies aside from investigating NK cell activity in experimental animals and humans included studies of perforin expression and modulation in this lymphocyte subset. As NK cell activity is modified by their environment, we showed clinical stage-dependent impairment of their activity and in vitro effect of different sera, Th1 cytokines, and their combination in breast cancer, Hodgkin's disease, and non-Hodgkin's lymphoma patients, especially with respect to metabolic and cell membrane changes of peripheral blood lymphocytes evaluated by spontaneous release of the enzyme lactate dehydrogenase (LDH) that led to the correction of the LDH enzyme release assay for natural cytotoxicity. By long-term immuno-monitoring of patients with malignancies, we also showed the kinetics of NK cell modulation during chemo-immunotherapy. In our more recent studies, we give data of NK function and novel families of NK cell receptor expression in healthy individuals that may be of help in NK cell profiling, by giving referent values of basic and cytokine-induced expression of some NK cell receptors either in evaluation of disease or in immuno-monitoring during cytokine therapy of patients with malignancies. Moreover, we give novel aspects of modulation of NK cell activity by cytokines approved for immunotherapy, IFN and IL-2, in melanoma and other malignancies with respect to alterations in new activating (NKG2D and CD161) and inhibitory (CD158a and CD158b) receptor characteristics and signaling molecules in CD16- and CD56-defined NK cells and their small immunoregulatory and large cytotoxic subsets in peripheral blood and lymph nodes, as NK cell-mediated killing of tumor cells depends on the balance between stimulatory and inhibitory signaling.

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Regulation of the expression of lactate dehydrogenase isozymes in human lymphocytes

Cited by 10 publications

References 23 publications

Nef-Mediated Lipid Raft Exclusion of UbcH7 Inhibits Cbl Activity in T Cells to Positively Regulate Signaling

Nef-Mediated Lipid Raft Exclusion of UbcH7 Inhibits Cbl Activity in T Cells to Positively Regulate Signaling

Different alterations in lactate dehydrogenase activity and profile of peripheral blood mononuclear cells in Hodgkin's and non‐Hodgkin's lymphomas

Investigation of NK cell function and their modulation in different malignancies

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