Skip to main content
SpringerLink
Log in

Role of Neutral Sphingomyelinases in Aging and Inflammation

  • Chapter
Lipids in Health and Disease

Part of the book series: Subcellular Biochemistry ((SCBI,volume 49))

Abstract

Aging is characterized by changes in the organism’s immune functions and stress response, which in the elderly leads to increased incidence of complications and mortality following inflammatory stress. Alterations in the neuro-endocrine axes and overall decline in the immune system play an essential role in this process. Overwhelming evidence however suggests that many cellular cytokine signaling pathways are also affected, thus underscoring the idea that both, “cellular” and “systemic” changes contribute to aging. IL-1β for example, induces more potent cellular responses in hepatocytes isolated from aged animals then in hepatocytes from young rats. This phenomenon is referred to as IL-1b hyperresponsiveness and is linked to abnormal regulation of various acute phase proteins during aging.

Evidence has consistently indicated that activation of neutral sphingomyelinase and the resulting accumulation of ceramide mediate cellular responses to LPS, IL-1β, and TNFα in young animals. More recent studies identified the cytokine-inducible neutral sphingomyelinase with nSMase2 (smpd3) that is localized in the plasma membrane and mediates cellular responses to IL-1β and TNFα. Intriguingly, constitutive up-regulation of nSMase2 occurs in aging and it underlies the hepatic IL-1b hyperresponsiveness. The increased activity of nSMases2 in aging is caused by a substantial decline in hepatic GSH content linking thereby oxidative stress to the onset of pro-inflammatory state in liver. nSMase2 apparently follows a pattern of regulation consisting with “developmental-aging” continuum, since in animal models of delayed aging, like calorie-restricted animals, the aging-associated changes in NSMase activity and function are reversed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abraham, C. R., Selkoe, D. J., and Potter, H. Immunochemical identification of the serine protease inhibitor alpha 1-antichymotrypsin in the brain amyloid deposits of Alzheimer's disease. Cell 52 (1988) 487–501.

    Article  PubMed  CAS  Google Scholar 

  • Acharya, U., Patel, S., Koundakjian, E., Nagashima, K., Han, X., and Acharya, J. K. Modulating sphingolipid biosynthetic pathway rescues photoreceptor degeneration. Science 299 (2003) 1740–1743.

    Article  PubMed  CAS  Google Scholar 

  • Adib-Conquy, M., and Cavaillon, J. M. Gamma interferon and granulocyte/monocyte colony-stimulating factor prevent endotoxin tolerance in human monocytes by promoting interleukin-1 receptor-associated kinase expression and its association to MyD88 and not by modulating TLR4 expression. J Biol Chem 277 (2002) 27927–27934.

    Article  PubMed  CAS  Google Scholar 

  • Algeri, S., Biagini, L., Bianchi, S., Garofalo, P., Marconi, M., Pitsikas, N., Raimondi, L., Sacchetti, G., Tacconi, M. T., Bertani, T., and et al. The effect of caloric restriction on a rat model of aging: biological, pathological, biochemical and behavioral characterization. Aging (Milano) 3 (1991) 388–390.

    CAS  Google Scholar 

  • Ayasolla, K., Khan, M., Singh, A. K., and Singh, I. Inflammatory mediator and beta-amyloid (25–35)-induced ceramide generation and iNOS expression are inhibited by vitamin E. Free Radic Biol Med 37 (2004) 325–338.

    Article  PubMed  CAS  Google Scholar 

  • Bello, R. I., Gomez-Diaz, C., Buron, M. I., Alcain, F. J., Navas, P., and Villalba, J. M. Enhanced anti-oxidant protection of liver membranes in long-lived rats fed on a coenzyme Q10-supplemented diet. Exp Gerontol 40 (2005) 694–706.

    Article  PubMed  CAS  Google Scholar 

  • Berk, B. C., Weintraub, W. S., and Alexander, R. W. Elevation of C-reactive protein in "active" coronary artery disease. Am J Cardiol 65 (1990) 168–172.

    Article  PubMed  CAS  Google Scholar 

  • Bonsall, M. B. Longevity and ageing: appraising the evolutionary consequences of growing old. Philos Trans R Soc Lond B Biol Sci 361 (2006) 119–135.

    Article  PubMed  Google Scholar 

  • Bose, C., Bhuvaneswaran, C., and Udupa, K. B. Age-related alteration in hepatic acyl-CoA: cholesterol acyltransferase and its relation to LDL receptor and MAPK. Mech Ageing Dev 126 (2005) 740–751.

    Article  PubMed  CAS  Google Scholar 

  • Cao, Z., Xiong, J., Takeuchi, M., Kurama, T., and Goeddel, D. V. TRAF6 is a signal transducer for interleukin-1. Nature 383 (1996) 443–446.

    Article  PubMed  CAS  Google Scholar 

  • Castillo, S. S., Levy, M., Thaikoottathil, J. V., and Goldkorn, T. Reactive nitrogen and oxygen species activate different sphingomyelinases to induce apoptosis in airway epithelial cells. Exp Cell Res 313 (2007) 2680–2686.

    Article  PubMed  CAS  Google Scholar 

  • Ceda, G. P., Dall'Aglio, E., Maggio, M., Lauretani, F., Bandinelli, S., Falzoi, C., Grimaldi, W., Ceresini, G., Corradi, F., Ferrucci, L., Valenti, G., and Hoffman, A. R. Clinical implications of the reduced activity of the GH-IGF-I axis in older men. J Endocrinol Invest 28 (2005) 96–100.

    PubMed  CAS  Google Scholar 

  • Chalfant, C. E., Kishikawa, K., Mumby, M. C., Kamibayashi, C., Bielawska, A., and Hannun, Y. A. Long chain ceramides activate protein phosphatase-1 and protein phosphatase-2A. Activation is stereospecific and regulated by phosphatidic acid. J Biol Chem 274 (1999) 20313–20317.

    Article  PubMed  CAS  Google Scholar 

  • Chen, J., Nikolova-Karakashian, M., Merrill, A. H., Jr., and Morgan, E. T. Regulation of cytochrome P450 2C11 (CYP2C11) gene expression by interleukin-1, sphingomyelin hydrolysis, and ceramides in rat hepatocytes. J Biol Chem 270 (1995) 25233–25238.

    Article  PubMed  CAS  Google Scholar 

  • Chung, H. Y., Kim, H. J., Kim, J. W., and Yu, B. P. The inflammation hypothesis of aging: molecular modulation by calorie restriction. Ann N Y Acad Sci 928 (2001) 327–335.

    Article  PubMed  CAS  Google Scholar 

  • Clarke, C. J., Snook, C. F., Tani, M., Matmati, N., Marchesini, N., and Hannun, Y. A. The Extended Family of Neutral Sphingomyelinases. Biochemistry 45 (2006) 11247–11256.

    Article  PubMed  CAS  Google Scholar 

  • Clarke, C. J., Truong, T. G., and Hannun, Y. A. Role for neutral sphingomyelinase-2 in tumor necrosis factor alpha-stimulated expression of vascular cell adhesion molecule-1 (VCAM) and intercellular adhesion molecule-1 (ICAM) in lung epithelial cells: p38 MAPK is an upstream regulator of nSMase2. J Biol Chem 282 (2007) 1384–1396.

    Article  PubMed  CAS  Google Scholar 

  • Claycombe, K. J., Wu, D., Nikolova-Karakashian, M., Palmer, H., Beharka, A., Paulson, K. E., and Meydani, S. N. Ceramide mediates age-associated increase in macrophage cyclooxygenase-2 expression. J Biol Chem 277 (2002) 30784–30791.

    Article  PubMed  CAS  Google Scholar 

  • Cuschieri, J., Gourlay, D., Garcia, I., Jelacic, S., and Maier, R. V. Implications of proteasome inhibition: an enhanced macrophage phenotype. Cell Immunol 227 (2004) 140–147.

    Article  PubMed  CAS  Google Scholar 

  • Cutler, R. G., and Mattson, M. P. Sphingomyelin and ceramide as regulators of development and lifespan. Mech Ageing Dev 122 (2001) 895–908.

    Article  PubMed  CAS  Google Scholar 

  • De Palma, C., Meacci, E., Perrotta, C., Bruni, P., and Clementi, E. Endothelial Nitric Oxide Synthase Activation by Tumor Necrosis Factor {alpha} Through Neutral Sphingomyelinase 2, Sphingosine Kinase 1, and Sphingosine 1 Phosphate Receptors: A Novel Pathway Relevant to the Pathophysiology of Endothelium. Arterioscler Thromb Vasc Biol 26 (2006) 99–105.

    Article  PubMed  CAS  Google Scholar 

  • Di Iorio, A., Ferrucci, L., Sparvieri, E., Cherubini, A., Volpato, S., Corsi, A., Bonafe, M., Franceschi, C., Abate, G., and Paganelli, R. Serum IL-1beta levels in health and disease: a population-based study. 'The InCHIANTI study'. Cytokine 22 (2003) 198–205.

    Article  PubMed  CAS  Google Scholar 

  • Fan, J., Molina, P. E., Gelato, M. C., and Lang, C. H. Differential tissue regulation of insulin-like growth factor-I content and binding proteins after endotoxin. Endocrinology 134 (1994) 1685–1692.

    Article  PubMed  CAS  Google Scholar 

  • Franceschi, C., Bonafe, M., Valensin, S., Olivieri, F., De Luca, M., Ottaviani, E., and De Benedictis, G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci 908 (2000) 244–254.

    PubMed  CAS  Google Scholar 

  • Franceschi, C., Capri, M., Monti, D., Giunta, S., Olivieri, F., Sevini, F., Panourgia, M. P., Invidia, L., Celani, L., Scurti, M., Cevenini, E., Castellani, G. C., and Salvioli, S. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128 (2007) 92–105.

    Article  PubMed  CAS  Google Scholar 

  • Goswami, R., Ahmed, M., Kilkus, J., Han, T., Dawson, S. A., and Dawson, G. Differential regulation of ceramide in lipid-rich microdomains (rafts): Antagonistic role of palmitoyl:protein thioesterase and neutral sphingomyelinase 2. J Neurosci Res 81 (2005) 208–217.

    Article  PubMed  CAS  Google Scholar 

  • Gouaze, V., Mirault, M. E., Carpentier, S., Salvayre, R., Levade, T., and Andrieu-Abadie, N. Glutathione peroxidase-1 overexpression prevents ceramide production and partially inhibits apoptosis in doxorubicin-treated human breast carcinoma cells. Mol Pharmacol 60 (2001) 488–496.

    PubMed  CAS  Google Scholar 

  • Hagen, T. M., Vinarsky, V., Wehr, C. M., and Ames, B. N. (R)-alpha-lipoic acid reverses the age-associated increase in susceptibility of hepatocytes to tert-butylhydroperoxide both in vitro and in vivo. Antioxid Redox Signal 2 (2000) 473–483.

    Article  PubMed  CAS  Google Scholar 

  • Han, D., Hosokawa, T., Aoike, A., and Kawai, K. Age-related enhancement of tumor necrosis factor (TNF) production in mice. Mech Ageing Dev 84 (1995) 39–54.

    Article  PubMed  CAS  Google Scholar 

  • Hannun, Y. A., and Obeid, L. M. The Ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind. J Biol Chem 277 (2002) 25847–25850.

    Article  PubMed  CAS  Google Scholar 

  • Hayashi, Y., Kiyono, T., Fujita, M., and Ishibashi, M. cca1 Is Required for Formation of Growth-arrested Confluent Monolayer of Rat 3Y1 Cells. J Biol Chem 272 (1997) 18082–18086.

    Article  PubMed  CAS  Google Scholar 

  • Hofmann, K., Tomiuk, S., Wolff, G., and Stoffel, W. Cloning and characterization of the mammalian brain-specific, Mg2+-dependent neutral sphingomyelinase. Proc Natl Acad Sci USA 97 (2000) 5895–5900.

    Article  PubMed  CAS  Google Scholar 

  • Hsieh, C. C., Xiong, W., Xie, Q., Rabek, J. P., Scott, S. G., An, M. R., Reisner, P. D., Kuninger, D. T., and Papaconstantinou, J. Effects of age on the posttranscriptional regulation of CCAAT/enhancer binding protein alpha and CCAAT/enhancer binding protein beta isoform synthesis in control and LPS-treated livers. Mol Biol Cell 9 (1998) 1479–1494.

    PubMed  CAS  Google Scholar 

  • Hsieh, C. C., Rosenblatt, J. I., and Papaconstantinou, J. Age-associated changes in SAPK/JNK and p38 MAPK signaling in response to the generation of ROS by 3-nitropropionic acid. Mech Ageing Dev 124 (2003) 733–746.

    Article  PubMed  CAS  Google Scholar 

  • Jenkins, G. M., and Hannun, Y. A. Role for de novo sphingoid base biosynthesis in the heat-induced transient cell cycle arrest of Saccharomyces cerevisiae. J Biol Chem 276 (2001) 8574–8581.

    Article  PubMed  CAS  Google Scholar 

  • Kalehua, A. N., Taub, D. D., Baskar, P. V., Hengemihle, J., Munoz, J., Trambadia, M., Speer, D. L., De Simoni, M. G., and Ingram, D. K. Aged mice exhibit greater mortality concomitant to increased brain and plasma TNF-alpha levels following intracerebroventricular injection of lipopolysaccharide. Gerontology 46 (2000) 115–128.

    Article  PubMed  CAS  Google Scholar 

  • Karakashian, A. A., Giltiay, N. V., Smith, G. M., and Nikolova-Karakashian, M. N. Expression of neutral sphingomyelinase-2 (NSMase-2) in primary rat hepatocytes modulates IL-beta-induced JNK activation. Faseb J 18 (2004) 968–970.

    PubMed  CAS  Google Scholar 

  • Kim, S., Kang, M., Choi, Y., Suh, Y., and Kim, D. Sphingomyelinase activity is enhanced in cerebral cortex of senescence-accelerated mouse-P/10 with advancing age. Biophys Biophim Res Comm 237 (1997) 583–587.

    Article  CAS  Google Scholar 

  • Kirkwood, T. B., and Austad, S. N. Why do we age? Nature 408 (2000) 233–238.

    Article  PubMed  CAS  Google Scholar 

  • Lang, C. H., Fan, J., Cooney, R., and Vary, T. C. IL-1 receptor antagonist attenuates sepsis-induced alterations in the IGF system and protein synthesis. Am J Physiol 270 (1996) E430–437.

    PubMed  CAS  Google Scholar 

  • Lang, C. H., Pollard, V., Fan, J., Traber, L. D., Traber, D. L., Frost, R. A., Gelato, M. C., and Prough, D. S. Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin. Am J Physiol 273 (1997) R371–378.

    PubMed  CAS  Google Scholar 

  • Lang, C. H., Nystrom, G. J., and Frost, R. A. Regulation of IGF binding protein-1 in hep G2 cells by cytokines and reactive oxygen species. Am J Physiol 276 (1999) G719–727.

    PubMed  CAS  Google Scholar 

  • Lecka-Czernik, B., Moerman, E., Jones, R., and Goldstein, S. Identification of gene sequences overexpressed in senescent and Werner syndrome human fibroblasts. Exp. Gerontology. 31 (1996) 159–174.

    Article  CAS  Google Scholar 

  • Lee, A., Whyte, M. K., and Haslett, C. Inhibition of apoptosis and prolongation of neutrophil functional longevity by inflammatory mediators. J Leukoc Biol 54 (1993) 283–288.

    PubMed  CAS  Google Scholar 

  • Li, L., Cousart, S., Hu, J., and McCall, C. E. Characterization of Interleukin-1 Receptor-associated Kinase in Normal and Endotoxin-tolerant Cells. J Biol Chem 275 (2000) 23340–23345.

    Article  PubMed  CAS  Google Scholar 

  • Lightle, S. A., Oakley, J. I., and Nikolova-Karakashian, M. N. Activation of sphingolipid turnover and chronic generation of ceramide and sphingosine in liver during aging. Mech Ageing Dev 120 (2000) 111–125.

    Article  PubMed  CAS  Google Scholar 

  • Liu, B., and Hannun, Y. A. Inhibition of the neutral magnesium-dependent sphingomyelinase by glutathione. J Biol Chem 272 (1997) 16281–16287.

    Article  PubMed  CAS  Google Scholar 

  • Liu, B., Andrieu-Abadie, N., Levade, T., Zhang, P., Obeid, L. M., and Hannun, Y. A. Glutathione regulation of neutral sphingomyelinase in tumor necrosis factor-alpha-induced cell death. J Biol Chem 273 (1998) 11313–11320.

    Article  PubMed  CAS  Google Scholar 

  • Lozanski, G., Berthier, F., and Kushner, I. The sphingomyelin-ceramide pathway participates in cytokine regulation of C-reactive protein and serum amyloid A, but not alpha-fibrinogen. Biochem J 328 (Pt 1) (1997) 271–275.

    PubMed  CAS  Google Scholar 

  • Luberto, C., Hassler, D. F., Signorelli, P., Okamoto, Y., Sawai, H., Boros, E., Hazen-Martin, D. J., Obeid, L. M., Hannun, Y. A., and Smith, G. K. Inhibition of Tumor Necrosis Factor-induced Cell Death in MCF7 by a Novel Inhibitor of Neutral Sphingomyelinase. J Biol Chem 277 (2002) 41128–41139.

    Article  PubMed  CAS  Google Scholar 

  • Marchesini, N., Osta, W., Bielawski, J., Luberto, C., Obeid, L. M., and Hannun, Y. A. Role for Mammalian Neutral Sphingomyelinase 2 in Confluence-induced Growth Arrest of MCF7 Cells. J Biol Chem 279 (2004) 25101–25111.

    Article  PubMed  CAS  Google Scholar 

  • Martin, S. F., Sawai, H., Villalba, J. M., and Hannun, Y. A. Redox regulation of neutral sphingomyelinase-1 activity in HEK293 cells through a GSH-dependent mechanism. Arch Biochem Biophys 459 (2007) 295–300.

    Article  PubMed  CAS  Google Scholar 

  • Mouton, R. E., and Venable, M. E. Ceramide induces expression of the senescence histochemical marker, beta-galactosidase, in human fibroblasts. Mech Ageing Dev 113 (2000) 169–181.

    Article  PubMed  CAS  Google Scholar 

  • Ninomiya-Tsuji, J., Kishimoto, K., Hiyama, A., Inoue, J., Cao, Z., and Matsumoto, K. The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway. Nature 398 (1999) 252–256.

    Article  PubMed  CAS  Google Scholar 

  • Petkova, D. H., Momchilova-Pankova, A. B., Markovska, T. T., and Koumanov, K. S. Age-related changes in rat liver plasma membrane sphingomyelinase activity. Exp Gerontol 23 (1988) 19–24.

    Article  PubMed  CAS  Google Scholar 

  • Pewzner-Jung, Y., Ben-Dor, S., and Futerman, A. H. When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?: Insights into the regulation of ceramide synthesis. J Biol Chem 281 (2006) 25001–25005.

    Article  PubMed  CAS  Google Scholar 

  • Puglielli, L., Ellis, B. C., Saunders, A. J., and Kovacs, D. M. Ceramide stabilizes beta-site amyloid precursor protein-cleaving enzyme 1 and promotes amyloid beta-peptide biogenesis. J Biol Chem 278 (2003) 19777–19783.

    Article  PubMed  CAS  Google Scholar 

  • Rabek, J. P., Scott, S., Hsieh, C. C., Reisner, P. D., and Papaconstantinou, J. Regulation of LPS-mediated induction of C/EBP delta gene expression in livers of young and aged mice. Biochim Biophys Acta 1398 (1998) 137–147.

    PubMed  CAS  Google Scholar 

  • Riebeling, C., Allegood, J. C., Wang, E., Merrill, A. H., Jr., and Futerman, A. H. Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors. J Biol Chem 278 (2003) 33735–33738.

    Article  CAS  Google Scholar 

  • Rosenthal, C. J., and Franklin, E. C. Variation with age and disease of an amyloid A protein-related serum component. J Clin Invest 55 (1975) 746–753.

    Article  PubMed  CAS  Google Scholar 

  • Rutkute, K., Asmis, R. H., and Nikolova-Karakashian, M. N. Regulation of neutral sphingomyelinase-2 by GSH: a new insight to the role of oxidative stress in aging-associated inflammation. J Lipid Res 48 (2007a) 2443–2452.

    Article  CAS  Google Scholar 

  • Rutkute, K., Karakashian, A. A., Giltiay, N. V., Dobierzewska, A., and Nikolova-Karakashian, M. N. Aging in rat causes hepatic hyperresponsiveness to interleukin 1 b which is mediated by neutral sphingomyelinase-2. Hepatology 46 (2007b) 1166–1176.

    Article  CAS  Google Scholar 

  • Rutkute, K., and Nikolova-Karakashian, M. N. Regulation of insulin-like growth factor binding protein-1 expression during aging. Biochem Biophys Res Commun 361 (2007c) 263–269.

    Article  CAS  Google Scholar 

  • Sawai, H., Domae, N., Nagan, N., and Hannun, Y. A. Function of the Cloned Putative Neutral Sphingomyelinase as Lyso-platelet Activating Factor-Phospholipase C. J Biol Chem 274 (1999) 38131–38139.

    Article  PubMed  CAS  Google Scholar 

  • Shirakabe, K., Yamaguchi, K., Shibuya, H., Irie, K., Matsuda, S., Moriguchi, T., Gotoh, Y., Matsumoto, K., and Nishida, E. TAK1 mediates the ceramide signaling to stress-activated protein kinase/c-Jun N-terminal kinase. J Biol Chem 272 (1997) 8141–8144.

    Article  PubMed  CAS  Google Scholar 

  • Sly, L. M., Krzesicki, R. F., Brashler, J. R., Buhl, A. E., McKinley, D. D., Carter, D. B., and Chin, J. E. Endogenous brain cytokine mRNA and inflammatory responses to lipopolysaccharide are elevated in the Tg2576 transgenic mouse model of Alzheimer's disease. Brain Res Bull 56 (2001) 581–588.

    Article  PubMed  CAS  Google Scholar 

  • Spaulding, C. C., Walford, R. L., and Effros, R. B. Calorie restriction inhibits the age-related dysregulation of the cytokines TNF-alpha and IL-6 in C3B10RF1 mice. Mech Ageing Dev 93 (1997) 87–94.

    Article  PubMed  CAS  Google Scholar 

  • Stoffel, W., Jenke, B., Block, B., Zumbansen, M., and Koebke, J. Neutral sphingomyelinase 2 (smpd3) in the control of postnatal growth and development. Proc Natl Acad Sci USA 102 (2005) 4554–4559.

    Article  PubMed  CAS  Google Scholar 

  • Suh, Y. Age-specific changes in expression, activity, and activation of the c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinases by methyl methanesulfonate in rats. Mech Ageing Dev 122 (2001) 1797–1811.

    Article  PubMed  CAS  Google Scholar 

  • Tang, Y., Di Pietro, L., Feng, Y., and Wang, X. Increased TNF-alpha and PGI(2), but not NO release from macrophages in 18-month-old rats. Mech Ageing Dev 114 (2000) 79–88.

    Article  PubMed  CAS  Google Scholar 

  • Tellier, E., Negre-Salvayre, A., Bocquet, B., Itohara, S., Hannun, Y. A., Salvayre, R., and Auge, N. Role for furin in tumor necrosis factor alpha-induced activation of the matrix metalloproteinase/sphingolipid mitogenic pathway. Mol Cell Biol 27 (2007) 2997–3007.

    Article  PubMed  CAS  Google Scholar 

  • Venable, M. E., Lee, J. Y., Smyth, M. J., Bielawska, A., and Obeid, L. M. Role of ceramide in cellular senescence. J Biol Chem 270 (1995) 30701–30708.

    Article  PubMed  CAS  Google Scholar 

  • Venkataraman, K., and Futerman, A. H. Do longevity assurance genes containing Hox domains regulate cell development via ceramide synthesis? FEBS Lett 528 (2002a) 3–4.

    Article  CAS  Google Scholar 

  • Venkataraman, K., Riebeling, C., Bodennec, J., Riezman, H., Allegood, J. C., Sullards, M. C., Merrill, A. H., Jr., and Futerman, A. H. Upstream of growth and differentiation factor 1 (uog1), a mammalian homolog of the yeast longevity assurance gene 1 (LAG1), regulates N-stearoyl-sphinganine (C18-(dihydro)ceramide) synthesis in a fumonisin B1-independent manner in mammalian cells. J Biol Chem 277 (2002b) 35642–35649.

    Article  CAS  Google Scholar 

  • Verheij, M., Bose, R., Lin, X. H., Yao, B., Jarvis, W. D., Grant, S., Birrer, M. J., Szabo, E., Zon, L. I., Kyriakis, J. M., Haimovitz-Friedman, A., Fuks, Z., and Kolesnick, R. N. Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 380 (1996) 75–79.

    Article  PubMed  CAS  Google Scholar 

  • Vericel, E., Narce, M., Ulmann, L., Poisson, J. P., and Lagarde, M. Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats. Mol Cell Biochem 132 (1994) 25–29.

    Article  PubMed  CAS  Google Scholar 

  • Walston, J., and Fried, L. P. Frailty and the older man. Med Clin North Am 83 (1999) 1173-1194.

    Article  PubMed  CAS  Google Scholar 

  • Wesche, H., Henzel, W. J., Shillinglaw, W., Li, S., and Cao, Z. MyD88: an adapter that recruits IRAK to the IL-1 receptor complex. Immunity 7 (1997) 837–847.

    Article  PubMed  CAS  Google Scholar 

  • Westwick, J. K., Bielawska, A. E., Dbaibo, G., Hannun, Y. A., and Brenner, D. A. Ceramide activates the stress-activated protein kinases. J Biol Chem 270 (1995) 22689–22692.

    Article  PubMed  CAS  Google Scholar 

  • Wu, D., Marko, M., Claycombe, K., Paulson, K. E., and Meydani, S. N. Ceramide-induced and age-associated increase in macrophage COX-2 expression is mediated through up-regulation of NF-kappa B activity. J Biol Chem 278 (2003) 10983–10992.

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto, K., Shimokawa, T., Yi, H., Isobe, K., Kojima, T., Loskutoff, D. J., and Saito, H. Aging accelerates endotoxin-induced thrombosis : increased responses of plasminogen activator inhibitor-1 and lipopolysaccharide signaling with aging. Am J Pathol 161 (2002) 1805–1814.

    PubMed  CAS  Google Scholar 

  • Yamin, T. T., and Miller, D. K. The interleukin-1 receptor-associated kinase is degraded by proteasomes following its phosphorylation. J Biol Chem 272 (1997) 21540–21547.

    Article  PubMed  CAS  Google Scholar 

  • Yang, J., Anzo, M., and Cohen, P. Control of aging and longevity by IGF-I signaling. Exp Gerontol 40 (2005) 867–872.

    Article  PubMed  CAS  Google Scholar 

  • Yu, Z. F., Nikolova-Karakashian, M., Zhou, D., Cheng, G., Schuchman, E. H., and Mattson, M. P. Pivotal role for acidic sphingomyelinase in cerebral ischemia-induced ceramide and cytokine production, and neuronal apoptosis. J Mol Neurosci 15 (2000) 85–97.

    Article  PubMed  CAS  Google Scholar 

  • Zerofsky, M., Harel, E., Silverman, N., and Tatar, M. Aging of the innate immune response in Drosophila melanogaster. Aging Cell 4 (2005) 103–108.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Lexington, University of Kentucky College of Medicine, KY, USA

    Mariana Nikolova-Karakashian

Authors
  1. Mariana Nikolova-Karakashian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander Karakashian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kristina Rutkute
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Biochemistry Department, King’s College London, 150 Stamford Street, London SE1 9NH, UK

    Peter J. Quinn

  2. State Key Laboratory of Food Science and Technology, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, China

    Xiaoyuan Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Springer Science+Business Media B.V.

About this chapter

Cite this chapter

Nikolova-Karakashian, M., Karakashian, A., Rutkute, K. (2008). Role of Neutral Sphingomyelinases in Aging and Inflammation. In: Quinn, P.J., Wang, X. (eds) Lipids in Health and Disease. Subcellular Biochemistry, vol 49. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8831-5_18

Download citation

Publish with us

Policies and ethics

Search

Navigation