Journal of Internal Medicine 1997; 242: 465-478Elevated apoptotic cell population in patients with chronic
fatigue syndrome: The pivotal role of protein kinase RNA
A. VOJDANIab , M. GHONEUMb , P.C. CHOPPAa
, L. MAGTOTOa & C. W. LAPPc
From the aImmunosciences Laboratory, Inc., Beverly Hills, and bCharles
Drew University School of Medicine and Science, Los Angeles, California, and the cHunter-Hopkins
Centre, Charlotte, North Carolina, USA
| Abstract. Vojdani
A, Ghoneum M, Choppa PC, Magtoto L, Lapp CW (Immunosciences Laboratory Inc., Beverly
Hills, and Charles Drew University School of Medicine and Science, Los Angeles,
California, and the Hunter-Hopkins Centre, Charlotte, North Carolina, USA). Elevated
apoptotic cell population in patients with chronic fatigue syndrome: the pivotal role of
protein kinase RNA. J Intern Med 1997; 242: 465-478. Objectives.
A prominent feature of chronic fatigue syndrome (CFS) is a disordered immune system.
Recent evidence indicates that induction of apoptosis might be mediated in a dysregulated
immune system by the upregulation of growth inhibitory cytokines. Therefore, the purpose
of this study was to evaluate the apoptotic cell population, interferon-alpha (IFN-a ) and
the IFN-induced protein kinase RNA (PKR) gene transcripts in peripheral blood lymphocytes
(PBL) of CFS individuals, as compared to healthy controls.
Subjects and methods. PBL were isolated from CFS (n
= 29) and healthy control individuals (n = 15) and subjected to quantitative analysis of
apoptotic cell population and cell cycle progression by flow cytometry. Quantitative
competitive polymerase chain reaction (Q/C PCR) and |
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Western blot analysis were
used to assess the levels of PKR mRNA and protein in control and CFS individuals. In
addition, circulating IFN-a was measured by ELISA assay. Results.
Increased apoptotic cell population was observed in CFS individuals, as compared
to healthy controls (26.6 ± 12.9% and 9.9 ± 4.2%, respectively). The increased apoptotic
subpopulation in CFS individuals was accompanied by an abnormal cell arrest in the S phase
and the G2/M boundary of the cell cycle as compared to the control group (8.6 ± 1.2 to
22.8 ± 2.4 and 3.6 ± 0.82 to 24.3 ± 3.4, respectively). In addition, CFS individuals
exhibited enhanced PKR mRNA and protein levels (mean basal level 3538 ± 1050 and 2.7 ±
0.26, respectively) as compared to healthy controls (mean basal level 562 ± 162 and 0.89
± 0.18, respectively). In 50% of the CFS samples (n = 29) treated with 2-aminopurine
(2-AP) (a potent inhibitor of PKR) the apoptotic population was reduced by more than 50%.
Conclusions. PKR-mediated apoptosis in CFS
individuals may contribute to the pathogenesis and the fatigue symptomatology associated
with CFS.
Keywords: apoptosis, chronic fatigue syndrome, PKR. |
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