Effect of overexpression of human Cu/Zn-SOD on activation-induced lymphocyte proliferation and apoptosis

Mohammad A. Pahlavani, James F. Mele, Arlan Richardson

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The process of lymphocyte proliferation and apoptosis is known to be linked to oxidative stress. In the present study, we have used a new transgenic mouse model to investigate the effect of human Cu/Zn superoxide dismutase (Cu/Zn-SOD) overexpression on activation-induced lymphocytes proliferation and apoptosis. Cu/Zn-SOD activity was 3.5-fold higher in the spleen of the transgenic mice overexpressing Cu/Zn-SOD (Tg-Cu/Zn-SOD) compared to the wild-type littermates. Proliferative response of lymphocytes to lipopolysaccharide (LPS), Concanavalin A (Con A), and anti-CD3 was measured by [3H]-thymidine incorporation. Activation-induced apoptosis was determined by incubating the T cells with anti-CD3 (primary stimulus) for 72 h, followed by restimulation with Con A (secondary stimulus) for various times. Apoptosis was assessed by measuring DNA fragmentation using a spectrofluorimetric assay and monitoring the expression of the specific apoptotic markers (Fas/CD95 receptor and Fas/CD95 ligand (Fas-L) using flow cytometry. There was no significant difference in proliferative response of lymphocytes to LPS, Con A, or anti-CD3 in transgenic mice overexpressing human Cu/Zn superoxide dismutase (Tg-Cu/Zn-SOD) compared to wild-type littermates. In addition, no significant difference was observed in lymphocyte populations and subsets between Tg-Cu/Zn-SOD mice and wild-type littermates. However, splenic T cells from Tg-Cu/Zn-SOD mice exhibited a significantly (p < .05) higher level of activation-induced DNA fragmentation than T cells from wild-type littermates. The increase in DNA fragmentation was paralleled with an increase in the proportion of T cells expressing Fas and Fas-L molecules. The possible consequences of Cu/Zn-SOD overproduction on activation-induced apoptosis are discussed.

Original languageEnglish (US)
Pages (from-to)1319-1327
Number of pages9
JournalFree Radical Biology and Medicine
Volume30
Issue number11
DOIs
StatePublished - Jun 1 2001

Fingerprint

Lymphocytes
Lymphocyte Activation
Chemical activation
Apoptosis
Fas Ligand Protein
T-cells
DNA Fragmentation
Concanavalin A
Transgenic Mice
T-Lymphocytes
Lipopolysaccharides
DNA
CD95 Antigens
Superoxide Dismutase
Superoxide Dismutase-1
Oxidative stress
Flow cytometry
Lymphocyte Subsets
Thymidine
Assays

Keywords

  • Apoptosis
  • Cu/Zn-SOD
  • Free radicals
  • Mitogenesis
  • Transgenic mice

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry

Cite this

Effect of overexpression of human Cu/Zn-SOD on activation-induced lymphocyte proliferation and apoptosis. / Pahlavani, Mohammad A.; Mele, James F.; Richardson, Arlan.

In: Free Radical Biology and Medicine, Vol. 30, No. 11, 01.06.2001, p. 1319-1327.

Research output: Contribution to journalArticle

Pahlavani, Mohammad A. ; Mele, James F. ; Richardson, Arlan. / Effect of overexpression of human Cu/Zn-SOD on activation-induced lymphocyte proliferation and apoptosis. In: Free Radical Biology and Medicine. 2001 ; Vol. 30, No. 11. pp. 1319-1327.
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