Age-dependent decrease of the lateral diffusion constant of proteins in the plasma membrane of hepatocytes as revealed by fluorescence recovery after photobleaching in tissue smears

Zs.‐Nagy, Imre; Kitani, Kenichi; Ohta, Minoru; Zs.-Nagy, Valéria; Imahori, Kazutomo

doi:10.1016/0167-4943(86)90016-6

Cited by 56 publications

(4 citation statements)

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“…Experimental data collectively indicate that the plasma membrane, via its special organization in lipid rafts, plays an important role in signal transduction via the TCR [35]. It has been known for some time, however, that there is an alteration in the physicochemical status of the plasma membrane, leading to increased rigidity and decreased fluidity with ageing [42]. This may well affect raft formation [43].…”

Section: Tcr and Costimulatory Signalling Changes With Ageing: A Biocmentioning

confidence: 99%

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Ageing, autoimmunity and arthritis: Perturbations of TCR signal transduction pathways with ageing – a biochemical paradigm for the ageing immune system

et al. 2003

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290 APC = antigen-presenting cell; DRM = detergent-resistant microdomain; ERK = extracellular signal-regulated kinase; IFN = interferon; IL = interleukin; ITAM = immunoreceptor tyrosine-based activation motif; LAT = linker of activated T cells; mAb = monoclonal antibody; MAPK = mitogenactivated protein kinase; MHC = major histocompatibility complex; NF = nuclear factor; NFAT = nuclear factor of activated T cells; PKC = protein kinase C; pLAT, tyrosine-phosphorylated LAT; PTK = protein tyrosine kinase; RA = rheumatoid arthritis; SLE = systemic lupus erythematosus; TCR = T-cell receptor; Th cells = T helper cells; ZAP = zeta-associated protein. Arthritis Research & TherapyVol 5 No 6 Fülöp et al. IntroductionIt is widely accepted that cell-mediated immune functions (cytotoxicity, delayed-type hypersensitivity, etc.) decline with age [1,2]. These age-associated immunological changes render an individual more susceptible to infection and possibly cancer, as well as to age-associated autoimmune disorders; they may also contribute to atherosclerosis and Alzheimer's disease [3][4][5]. There is still no clear consensus as to why cell-mediated immunity declines with age. It is generally believed that age-related immune deficiency develops coincident with the gradual involution of the thymus gland and, consequently, that thymic-related (T-cell) functions are the most profoundly affected. It has recently been suggested that the alterations observed with ageing are a reflection of an accumulation of relatively inert memory T cells and a consequent AbstractIt is widely accepted that cell-mediated immune functions decline with age, rendering an individual more susceptible to infection and possibly cancer, as well as to age-associated autoimmune diseases. The exact causes of T-cell functional decline are not known. One possible cause could be the development of defects in the transduction of mitogenic signals following TCR stimulation. This T-cell hyporesponsiveness due to defects of signalling through the TCR either from healthy elderly subjects or from individuals with autoimmune diseases such as rheumatoid arthritis or systemic lupus erythematosus results in an impaired ability to mount efficient immune responses and to maintain responsiveness to foreign antigens. This implies that a high proportion of autoreactive T cells might accumulate either intrathymically or in the periphery. T-cell anergy and differential TCR signalling could thus also be key players in the disruption of tolerance and the onset of autoimmune diseases. The increasing number of the elderly may lead to an increase of clinically important autoimmune diseases. We will review the signal transduction changes through the TCR-CD3 complex in T lymphocytes from healthy elderly subjects, which result in a modification of the activation of transcription factors involved in IL-2 gene expression leading to decreased IL-2 production. The putative contribution of altered T-cell signalling with ageing in the development of autoimmune diseases will be also discussed.

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Section: Tcr and Costimulatory Signalling Changes With Ageing: A Biocmentioning

confidence: 99%

“…However, this could be independent of TCR activation. Furthermore, the alteration in the membrane composition and fluidity due to increased cholesterol content could provide an explanation for these signalling alterations [42,49]. …”

Section: Putative Contribution Of Tcr Signalling Changes In Ageing Tomentioning

confidence: 99%

Ageing, autoimmunity and arthritis: Perturbations of TCR signal transduction pathways with ageing – a biochemical paradigm for the ageing immune system

et al. 2003

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“…The lateral mobility of membrane proteins and lipids was measured using fluorescence recovery after the photobleaching (FRAP) technique 50. The lateral diffusion constant of hepatocyte membrane proteins ( D p ) displays a characteristic negative linear‐age correlation in Fischer 34450,51 and Wistar52 rats, in C57BL black mice,53 in wild mouse strains of considerably different longevity ( Peromyscus leucopus, Mus musculus ),54 BN/Bi rats,55 as well as SAM mice 56. The same finding has been described for the ConA‐receptor proteins in the skeletal muscle cells of mice57 and in the large brain cortical cells of rats 58.…”

Section: In Vivo Biological Effects Of Cph and Bce‐001mentioning

confidence: 99%

Pharmacological Interventions against Aging through the Cell Plasma Membrane

Zs.‐Nagy

2002

Annals of the New York Academy of Sciences

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As was shown in a recent review by this author (Ann. N.Y. Acad. Sci., 928: 187-199, 2001), oxyradicals cannot be considered only as harmful by-products of the oxidative metabolism, but living cells and organisms implicitly require their production. This idea is supported by numerous facts and arguments, the most important of which is that the complete inhibition of the oxyradical production by KCN (or by any block of respiration) kills the living organisms long before the energy reserves would be exhausted. This new theoretical approach not only helps our understanding of the normal functions of the living organisms, such as the basic memory mechanisms in the brain cells, but also helps in identifying the site-specific, radical-induced damaging mechanisms that represent the undesirable side effects of oxygen free radicals. First of all, these effects make the cell plasma membrane vulnerable and cause a series of intracellular functional disorders, as described by the membrane hypothesis of aging (MHA). The logical way for any antiaging intervention therefore should be to increase the available number of loosely bound electrons inside the plasma membrane that are easily accessible for OH(*) free radical scavenging. The present review summarizes the available knowledge regarding the theory of the use of membrane-related antiaging pharmaca, like centrophenoxine (CPH), tested in both animal experiments and human clinical trials. A modified, developed version of CPH coded as BCE-001 is also reported.

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“…We have shown that one of the basic alterations could be a decrease in p56 lck activity in T lymphocytes of elderly subjects 4. In addition, there is an alteration in the membrane physicochemical status, leading to increased rigidity and decreased fluidity with aging 5. Recently, it was shown that localization of LAT was altered in immune synapses with aging in mice 6.…”

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confidence: 99%