PMID- 9169522
OWN - NLM
STAT- MEDLINE
DCOM- 19970630
LR  - 20220408
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 17
IP  - 12
DP  - 1997 Jun 15
TI  - Calcium homeostasis and reactive oxygen species production in cells transformed 
      by mitochondria from individuals with sporadic Alzheimer's disease.
PG  - 4612-22
AB  - Alzheimer's disease (AD) is associated with defects in mitochondrial function. 
      Mitochondrial-based disturbances in calcium homeostasis, reactive oxygen species 
      (ROS) generation, and amyloid metabolism have been implicated in the 
      pathophysiology of sporadic AD. The cellular consequences of mitochondrial 
      dysfunction, however, are not known. To examine these consequences, 
      mitochondrially transformed cells (cybrids) were created from AD patients or 
      disease-free controls. Mitochondria from platelets were fused to rho0 cells 
      created by depleting the human neuroblastoma line SH-SY5Y of its mitochondrial 
      DNA (mtDNA). AD cybrids demonstrated a 52% decrease in electron transport chain 
      (ETC) complex IV activity but no difference in complex I activity compared with 
      control cybrids or SH-SY5Y cells. This mitochondrial dysfunction suggests a 
      transferable mtDNA defect associated with AD. ROS generation was elevated in the 
      AD cybrids. AD cybrids also displayed an increased basal cytosolic calcium 
      concentration and enhanced sensitivity to inositol-1,4, 5-triphosphate 
      (InsP3)-mediated release. Furthermore, they recovered more slowly from an 
      elevation in cytosolic calcium induced by the InsP3 agonist carbachol. 
      Mitochondrial calcium buffering plays a major role after this type of 
      perturbation. beta-amyloid (25-35) peptide delayed the initiation of calcium 
      recovery to a carbachol challenge and slowed the recovery rate. Nerve growth 
      factor reduced the carbachol-induced maximum and moderated the recovery kinetics. 
      Succinate increased ETC activity and partially restored the AD cybrid recovery 
      rate. These subtle alterations in calcium homeostasis and ROS generation might 
      lead to increased susceptibility to cell death under circumstances not ordinarily 
      toxic.
FAU - Sheehan, J P
AU  - Sheehan JP
AD  - Department of Neurological Surgery, University of Virginia, Charlottesville, 
      Virginia 22908, USA.
FAU - Swerdlow, R H
AU  - Swerdlow RH
FAU - Miller, S W
AU  - Miller SW
FAU - Davis, R E
AU  - Davis RE
FAU - Parks, J K
AU  - Parks JK
FAU - Parker, W D
AU  - Parker WD
FAU - Tuttle, J B
AU  - Tuttle JB
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Adenine Nucleotides)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Multienzyme Complexes)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 1.- (Oxidoreductases)
RN  - EC 1.3.5.1 (Electron Transport Complex II)
RN  - EC 1.3.99.1 (Succinate Dehydrogenase)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenine Nucleotides/metabolism
MH  - Aged
MH  - Alzheimer Disease/*metabolism
MH  - Blood Platelets/metabolism
MH  - Calcium/*metabolism
MH  - Cytosol/metabolism
MH  - DNA, Mitochondrial/genetics
MH  - Electron Transport
MH  - Electron Transport Complex II
MH  - Electron Transport Complex IV/metabolism
MH  - Female
MH  - Homeostasis
MH  - Humans
MH  - Kinetics
MH  - Male
MH  - Membrane Fusion
MH  - Middle Aged
MH  - Mitochondria/*metabolism/*transplantation
MH  - Multienzyme Complexes/metabolism
MH  - NAD(P)H Dehydrogenase (Quinone)/metabolism
MH  - Neuroblastoma
MH  - Oxidoreductases/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Reference Values
MH  - Succinate Dehydrogenase/metabolism
MH  - Tumor Cells, Cultured
PMC - PMC6573324
EDAT- 1997/06/15 00:00
MHDA- 1997/06/15 00:01
PMCR- 1997/12/15
CRDT- 1997/06/15 00:00
PHST- 1997/06/15 00:00 [pubmed]
PHST- 1997/06/15 00:01 [medline]
PHST- 1997/06/15 00:00 [entrez]
PHST- 1997/12/15 00:00 [pmc-release]
AID - 10.1523/JNEUROSCI.17-12-04612.1997 [doi]
PST - ppublish
SO  - J Neurosci. 1997 Jun 15;17(12):4612-22. doi: 10.1523/JNEUROSCI.17-12-04612.1997.