Skip to main content
×
Home
    • Aa
    • Aa
  • Access
  • Cited by 8
  • Cited by
    This article has been cited by the following publications. This list is generated based on data provided by CrossRef.

    Jackson, Rebecca A. Nguyen, Mai Linh Barrett, Angela N. Tan, Yuan Yee Choolani, Mahesh A. and Chen, Ee Sin 2016. Synthetic combinations of missense polymorphic genetic changes underlying Down syndrome susceptibility. Cellular and Molecular Life Sciences,


    Liao, Xing Li, Yan Gao, Ru Geng, Yan Chen, Xue Liu, Xue Ding, Yu Mu, Xin Wang, Ying and He, Jun 2015. Folate Deficiency Decreases Apoptosis of Endometrium Decidual Cells in Pregnant Mice via the Mitochondrial Pathway. Nutrients, Vol. 7, Issue. 3, p. 1916.


    Abe, Ikumi Shirato, Ken Hashizume, Yoko Mitsuhashi, Ryosuke Kobayashi, Ayumu Shiono, Chikako Sato, Shogo Tachiyashiki, Kaoru and Imaizumi, Kazuhiko 2013. Folate-deficiency induced cell-specific changes in the distribution of lymphocytes and granulocytes in rats. Environmental Health and Preventive Medicine, Vol. 18, Issue. 1, p. 78.


    Arigony, Ana Lúcia Vargas de Oliveira, Iuri Marques Machado, Miriana Bordin, Diana Lilian Bergter, Lothar and Pêgas Henriques, João Antonio 2013. The Influence of Micronutrients in Cell Culture: A Reflection on Viability and Genomic Stability. BioMed Research International, Vol. 2013, p. 1.


    Liang, Yan Li, Yuanyuan Li, Zhengli Liu, Zhuo Zhang, Zhiping Chang, Shaoyan and Wu, Jianxin 2012. Mechanism of folate deficiency-induced apoptosis in mouse embryonic stem cells: Cell cycle arrest/apoptosis in G1/G0 mediated by microRNA-302a and tumor suppressor gene Lats2. The International Journal of Biochemistry & Cell Biology, Vol. 44, Issue. 11, p. 1750.


    Tomek, Mary Akiyama, Toru and Dass, Crispin R. 2012. Role of Bcl-2 in tumour cell survival and implications for pharmacotherapy. Journal of Pharmacy and Pharmacology, Vol. 64, Issue. 12, p. 1695.


    Tang, Cai Zhang, Zhili Xu, Bo Li, Min Liu, Junyi and Cui, Jingrong 2008. Two newly synthesized 5-methyltetrahydrofolate-like compounds inhibit methionine synthase activity accompanied by cell cycle arrest in G1/S phase and apoptosis in vitro. Anti-Cancer Drugs, Vol. 19, Issue. 7, p. 697.


    Wu, Tong-Guo Li, Wei-Hong Lin, Zi-Qing and Wang, Le-Xin 2008. Effects of Folic Acid on Cardiac Myocyte Apoptosis in Rats with Streptozotocin-induced Diabetes Mellitus. Cardiovascular Drugs and Therapy, Vol. 22, Issue. 4, p. 299.


    ×

In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes

  • Hui-Li Lin (a1), Chung-Jern Chen (a2), Wen-Chan Tsai (a2), Jeng-Hsien Yen (a2) and Hong-Wen Liu (a2)
  • DOI: http://dx.doi.org/10.1079/BJN20051579
  • Published online: 01 March 2007
Abstract

In vitro folate deficiency is associated with S phase accumulation and apoptosis in various cell types. To investigate the role of p53 and two apoptosis-related molecules, bcl-2 and Fas antigen (Apo-1, CD95), in the mechanism whereby folate-deficient lymphocytes accumulate and undergo apoptosis in the S phase, normal human peripheral blood lymphocytes were cultured for 3–9 d in control medium or in specially ordered and formulated HAM’ F-10 medium lacking folic acid, thymidine and hypoxanthine. Cells were stimulated with phytohaemagglutinin for the final 72 h prior to harvesting. The results indicate that p53 expression was downregulated in folate-deficient lymphocytes when compared with the control lymphocytes during the relevant period of S phase accumulation and apoptosis. In addition, folate deficiency was also found to downregulate IL-2, Fas antigen and bcl-2 expression, in terms of either mRNA or protein levels. The downregulation of Fas antigen suggests that folate deficiency-induced apoptosis probably does not occur via the Fas pathway. As IL-2 is a known inducer of bcl-2, and the downregulation of bcl-2 induces apoptosis, the downregulation of IL-2 and bcl-2 is suggested to play an important role in apoptosis. The complete rescue of folate-deficient lymphocytes from apoptosis was achieved by folic acid, thymidine or hypoxanthine alone or thymidine and hypoxanthine in combination. These results suggest that IL-2 depletion by folate deficiency in lymphocytes reduces the bcl-2 level, thereby triggering deoxynucleoside triphosphate pool imbalance and p53-independent apoptosis.

    • Send article to Kindle

      To send this article to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes
      Your Kindle email address
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      In vitro folate deficiency induces apoptosis by a p53, Fas (Apo-1, CD95) independent, bcl-2 related mechanism in phytohaemagglutinin-stimulated human peripheral blood lymphocytes
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: Dr Hong-Wen Liu, fax +886 7 3215842, email liuhow@kmu.edu.tw
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

D Bunout , M Petermann , S Hirsch , P de la Maza , M Suazo , G Barrera & R Kauffman Low serum folate but normal homocysteine levels in patients with atherosclerotic vascular disease and matched healthy controls. Nutr 2000 16 434438

MK Collins , J Marvel , P Malde & A Lopez-Rivas Interleukin 3 protects murine bone marrow cells from apoptosis induced by DNA damaging agents. J Exp Med 1992 176 10431051

A Fleischer , V Ayllon , L Dumoutier , JC Renauld & A Rebollo Proapoptotic activity of ITM2B(s), a BH3-only protein induced upon IL-2-deprivation which interacts with Bcl-2. Oncogene 2002 21 31813189

A Fleming & AJ Copp Embryonic folate metabolism and mouse neural tube defects. Science 1998 280 21072109

JL Freudenheim , S Graham , JR Marshall , BP Haughey , S Cholewinski & G Wilkinson Folate intake and carcinogenesis of the colon and rectum. Int J Epidemiol 1991 20 368374

DA Hildeman , Y Zhu , TC Mitchell , J Kappler & P Marrack Molecular mechanisms of activated T cell death in vivo. Curr Opin Immunol 2002 14 354359

SJ James , BJ Miller , LJ McGarrity & SM Morris The effect of folic acid deficiency on deoxyribonucleotide pools and cell cycle distribution in mitogen-stimulated lymphocytes. Cell Prolif 1994 27 395406

SJ Kuerbitz , BS Plunkett , WV Walsh & MB Kastan Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci USA 1992 89 74917495

SP Linke , KC Clarkin , A Di Leonardo , A Tsou & GM Wahl A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev 1996 10 934947

SW Lowe , EM Schmitt , SW Smith , BA Osborne & T Jacks p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature 1993 362 847849

W Maltzman & L Czyzyk UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol Cell Biol 1984 4 16891694

ST Mashiyama , C Courtemanche , I Elson-Schwab , J Crott , BL Lee , CN Ong , M Fenech & BN Ames Uracil in DNA, determined by an improved assay, is increased when deoxynucleosides are added to folate-deficient cultured human lymphocytes. Anal Biochem 2004 330 5869

LK Michalis , K Pappas , A Tweddel , N Kolaitis , CS Katsouras , S Loukas , J Goudevenos & K Bourantas DA Sideris Relatively low red cell folate levels and acute coronary syndromes. Coron Artery Dis 2001 12 665668

FJ Oliver , MK Collins & A Lopez-Rivas Regulation of the salvage pathway of deoxynucleotides synthesis in apoptosis induced by growth factor deprivation. Biochem J 1996 316 421425

FJ Oliver , J Marvel , MK Collins & A Lopez-Rivas Bcl-2 oncogene protects a bone marrow-derived pre-B-cell line from 5 fluor,2deoxyuridine-induced apoptosis Biochem Biophys Res Commun 1993 194 126132

B Shane & EL Stokstad Vitamin B12-folate interrelationships. Annu Rev Nutr 1985 5 115141

RW Smithells , S Sheppard & CJ Schorah Vitamin deficiencies and neural tube defects. Arch Dis Child 1976 51 944950

MB van der Weyden , RJ Hayman , IS Rose & J Brumley Folatedeficient human lymphoblasts: changes in deoxynucleotide metabolism and thymidylate cycle activities. Eur J Haematol 1991 47 109114

HS Yu , WT Liao , KL Chang , CL Yu & GS Chen Arsenic induces TNF-a release and tumor necrosis factor receptor-1 signaling in T-helper cell apoptosis. J Invest Dermatol 2002 119 812819

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords: