Deficiency of chaperonin 60 in Down's syndrome.
Patients with Down syndrome (DS) and Alzheimer's disease (AD) share a number of characteristic neuropathologic lesions. Several lines of evidence suggest that mitochondria and the oxidative stress response are involved in the pathogenesis of both conditions. In the process of investigating the stress response in DS, we discovered a defective basal expression of a major mitochondrial heat shock protein, chaperonin 60 (Cpn60) in non-transformed dermal fibroblast cell lines from DS individuals. Such a defect was not present in control cells that had been cultured under identical physiological growth conditions. A quantitative analysis by Western blots showed a marked reduction of Cpn60 per equal amount of total protein in DS cells to an average of 35% of normal. Northern blot studies confirmed the defect and also showed a marked reduction of the mRNA signal for Cpn60 in all the DS cell lines. To gain further information, experiments were conducted to study the rate of de-novo synthesis of Cpn60 at normal and supraoptimal temperatures in DS and controls. Results showed no significant differences between the two study groups. HSP60 is important in mitochondrial function and defects in these organelles have been reported in DS and AD. Thus, the findings may have potential implications in the neuropathology of DS.
Bozner
Peter
P
Department of Pathology, University of South Alabama, Mobile, AL 36617, USA.
Wilson
G Lee
GL
Druzhyna
Nadya M
NM
Bryant-Thomas
Tara K
TK
LeDoux
Susan P
SP
Wilson
Glenn L
GL
Pappolla
Miguel A
MA
D000328:Adult; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology; D015152:Blotting, Northern; D015153:Blotting, Western; D002460:Cell Line; D018834:Chaperonin 60 / Q000235:genetics*; D002675:Child, Preschool; D004314:Down Syndrome / Q000235:genetics* / Q000473:pathology; D005347:Fibroblasts / Q000473:pathology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics
D018834:Chaperonin 60; D012333:RNA, Messenger