Age‐dependent variations in the expression of PLC isoforms upon mitogenic stimulation of peripheral blood T cells from healthy donors

The activation of phosphoinositide‐specific phospholipase C (PLC) is one of the early responses to various growth factors and it is known that these functions are altered with ageing. In the present investigation, the expression and cellular distribution of PLC isoenzymes in immunocompetent T lymphocytes from a test group of healthy individuals over 65 years old and a comparison group of healthy donors below 30 years old were compared using Western blot and confocal microscopy. All lymphocyte samples responded biochemically to phytohaemagglutinin (PHA) stimulation, as shown by at least 10‐fold increases in the β3 isoform and nuclear translocation of the β1, β2, β3, β4, γ1 and γ2 isoforms; however, consistent differences in the expression of the β2 isoform in unstimulated T cells and of the β2 and γ2 isoforms in stimulated T cells suggest that altered functions of the PLC pathway may have an age‐dependent impact on signal transduction events.

[1]  R. Pietro,et al.  Immunocytochemical Localization of Phospholipase C Isozymes in Cord Blood and Adult T-lymphocytes , 1999, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[2]  S. Rhee,et al.  Inositides in the nucleus: presence and characterisation of the isozymes of phospholipase beta family in NIH 3T3 cells. , 1999, Biochimica et Biophysica Acta.

[3]  U. Ponnappan,et al.  Decreased association of p56lck with CD4 may account for lowered tyrosine kinase activity in mitogen-activated human T lymphocytes during aging. , 1998, Cellular immunology.

[4]  S. Ryu,et al.  Localization of two forms of phospholipase C-beta1, a and b, in C6Bu-1 cells. , 1998, Biochimica et biophysica acta.

[5]  Michael F. Moran,et al.  Requirement for Phospholipase C-γ1 Enzymatic Activity in Growth Factor-Induced Mitogenesis , 1998, Molecular and Cellular Biology.

[6]  A. Fields,et al.  A Role for Nuclear Phosphatidylinositol-specific Phospholipase C in the G2/M Phase Transition* , 1997, The Journal of Biological Chemistry.

[7]  S. Capitani,et al.  Intranuclear translocation of phospholipase C beta2 during HL-60 myeloid differentiation. , 1997, Biochemical and biophysical research communications.

[8]  S. Rhee,et al.  Regulation of Phosphoinositide-specific Phospholipase C Isozymes* , 1997, The Journal of Biological Chemistry.

[9]  H. Hsu,et al.  Increased apoptosis of CD45RO− T cells with aging , 1997, Mechanisms of Ageing and Development.

[10]  K. Hirokawa,et al.  Impairment of signal transduction in T cells from old mice , 1997, Mechanisms of Ageing and Development.

[11]  S. Rhee,et al.  The Role of Carboxyl-terminal Basic Amino Acids in Gqα-dependent Activation, Particulate Association, and Nuclear Localization of Phospholipase C-β1* , 1996, The Journal of Biological Chemistry.

[12]  D. Noh,et al.  Phosphoinositide-specific phospholipase C and mitogenic signaling. , 1995, Biochimica et biophysica acta.

[13]  G. Pawelec.  Molecular and cell biological studies of ageing and their application to considerations of T lymphocyte immunosenescence , 1995, Mechanisms of Ageing and Development.

[14]  J. Jolles,et al.  Phosphoinositide metabolism, aging and Alzheimer's disease. , 1994, Biochimica et biophysica acta.

[15]  L. Cocco,et al.  Age-related events in human active T lymphocytes: changes in the phosphoinositidase C activity. , 1993, Biochemical and biophysical research communications.

[16]  A. Martelli,et al.  Nuclear localization and signalling activity of phosphoinositidase Cβ in Swiss 3T3 cells , 1992, Nature.

[17]  R. Irvine.  Inositol lipids in cell signalling , 1992, Current Biology.

[18]  M. Vitale,et al.  High-resolution detection of newly synthesized DNA by anti-bromodeoxyuridine antibodies identifies specific chromatin domains. , 1990, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[19]  H. Müller-Hermelink,et al.  Admission criteria for immunogerontological studies in man: The senieur protocol , 1984, Mechanisms of Ageing and Development.

[20]  D. Papermaster,et al.  Rapid embedding of tissues in Lowicryl K4M for immunoelectron microscopy. , 1984, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[21]  Y. Nishizuka.  Turnover of inositol phospholipids and signal transduction. , 1984, Science.

[22]  E. Dupont,et al.  The active T rosette: an early marker for T-cell activation. , 1982, Annales d'immunologie.

[23]  R. Rana,et al.  Age-related defect of phospholipase C activity, differential expression of the beta 2 isoform in active T lymphocytes from aged humans. , 1998, Human immunology.