A Dopaminergic Cell Line Variant Resistant to the Neurotoxin 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine

A Dopaminergic Cell Line Variant Resistant to the Neurotoxin... 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is known to cause parkinsonism by killing dopaminergic neurons; the toxic substance is a metabolite, 1‐methyl‐4‐phenylpyridinium ion (MPP+). PC12 cells, which are dopaminergic, are killed in culture by MPTP and MPP+ but at concentrations much higher than that required to kill affected neurons in vivo. However, at low concentrations (10–100 μM), MPP+ caused an increased production of lactate by PC12 cells. MPP+‐treated PC12 cells exhibited decreased mitochondrial respiration. Mitochondria from the treated cells respired normally in the presence of added succinate but not β‐hydroxybutyrate, a finding indicating that MPP+ inhibits the oxidation of some substrates selectively. MPP+ was more effective in killing the cells when glycolysis was reduced with 2‐deoxyglucose or by lowering the glucose content of the culture medium. Under these conditions, MPP+ inhibited ATP synthesis and depleted cellular stores of ATP. A PC12 variant that is even more resistant to MPTP and MPP+ than are wild‐type cells has been isolated. The MPTP‐resistant variant is also more resistant to the lethal effects of oligomycin, antimycin A, and rotenone. This variant exhibited altered lactate production and mitochondrial respiration. It is suggested that some brain neurons that accumulate MPP+ without being killed by it may also have an energy metabolism somewhat different from that of more sensitive neurons. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

A Dopaminergic Cell Line Variant Resistant to the Neurotoxin 1‐Methyl‐4‐Phenyl‐1,2,3,6‐Tetrahydropyridine

Loading next page...
 
/lp/wiley/a-dopaminergic-cell-line-variant-resistant-to-the-neurotoxin-1-methyl-gXSVeZI5ZO
Publisher
Wiley
Copyright
Copyright © 1987 Wiley Subscription Services, Inc., A Wiley Company
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1111/j.1471-4159.1987.tb02909.x
Publisher site
See Article on Publisher Site

Abstract

1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) is known to cause parkinsonism by killing dopaminergic neurons; the toxic substance is a metabolite, 1‐methyl‐4‐phenylpyridinium ion (MPP+). PC12 cells, which are dopaminergic, are killed in culture by MPTP and MPP+ but at concentrations much higher than that required to kill affected neurons in vivo. However, at low concentrations (10–100 μM), MPP+ caused an increased production of lactate by PC12 cells. MPP+‐treated PC12 cells exhibited decreased mitochondrial respiration. Mitochondria from the treated cells respired normally in the presence of added succinate but not β‐hydroxybutyrate, a finding indicating that MPP+ inhibits the oxidation of some substrates selectively. MPP+ was more effective in killing the cells when glycolysis was reduced with 2‐deoxyglucose or by lowering the glucose content of the culture medium. Under these conditions, MPP+ inhibited ATP synthesis and depleted cellular stores of ATP. A PC12 variant that is even more resistant to MPTP and MPP+ than are wild‐type cells has been isolated. The MPTP‐resistant variant is also more resistant to the lethal effects of oligomycin, antimycin A, and rotenone. This variant exhibited altered lactate production and mitochondrial respiration. It is suggested that some brain neurons that accumulate MPP+ without being killed by it may also have an energy metabolism somewhat different from that of more sensitive neurons.

Journal

Journal of NeurochemistryWiley

Published: Aug 1, 1987

References

  • PC12 variants deficient in catecholamine transport
    Bitler, Bitler; Zhang, Zhang; Howard, Howard
  • Metabolic pools of ATP in cultured bovine adrenal medullary chromaffin cells
    Corcoran, Corcoran; Korner, Korner; Caughey, Caughey; Kirshner, Kirshner
  • Sites of inhibition of mitochondrial electron transport in macrophage‐injured neoplastic cells
    Granger, Granger; Lehninger, Lehninger
  • Characterization of xylamine binding to proteins of PC12 pheochromocytoma cells
    Koide, Koide; Cho, Cho; Howard, Howard
  • Studies on the neurotoxicity of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine: inhibition of NAD‐linked substrate oxidation by its metabolite, 1‐methyl‐4‐phenylpyridinium
    Vyas, Vyas; Heikkila, Heikkila; Nicklas, Nicklas

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off