PMID- 10329961
OWN - NLM
STAT- MEDLINE
DCOM- 19990607
LR  - 20190122
IS  - 0002-9513 (Print)
IS  - 0002-9513 (Linking)
VI  - 276
IP  - 5
DP  - 1999 May
TI  - Importance of glucose-6-phosphate dehydrogenase activity in cell death.
PG  - C1121-31
LID - 10.1152/ajpcell.1999.276.5.C1121 [doi]
AB  - The intracellular redox potential plays an important role in cell survival. The
      principal intracellular reductant NADPH is mainly produced by the pentose
      phosphate pathway by glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting
      enzyme, and by 6-phosphogluconate dehydrogenase. Considering the importance of
      NADPH, we hypothesized that G6PDH plays a critical role in cell death. Our
      results show that 1) G6PDH inhibitors potentiated H2O2-induced cell death; 2)
      overexpression of G6PDH increased resistance to H2O2-induced cell death; 3) serum
      deprivation, a stimulator of cell death, was associated with decreased G6PDH
      activity and resulted in elevated reactive oxygen species (ROS); 4) additions of 
      substrates for G6PDH to serum-deprived cells almost completely abrogated the
      serum deprivation-induced rise in ROS; 5) consequences of G6PDH inhibition
      included a significant increase in apoptosis, loss of protein thiols, and
      degradation of G6PDH; and 6) G6PDH inhibition caused changes in mitogen-activated
      protein kinase phosphorylation that were similar to the changes seen with H2O2.
      We conclude that G6PDH plays a critical role in cell death by affecting the redox
      potential.
FAU - Tian, W N
AU  - Tian WN
AD  - Renal Division and Department of Medicine, Joslin Diabetes Center, Beth Israel
      Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115,
      USA.
FAU - Braunstein, L D
AU  - Braunstein LD
FAU - Apse, K
AU  - Apse K
FAU - Pang, J
AU  - Pang J
FAU - Rose, M
AU  - Rose M
FAU - Tian, X
AU  - Tian X
FAU - Stanton, R C
AU  - Stanton RC
LA  - eng
GR  - DK-09265-02/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Physiol
JT  - The American journal of physiology
JID - 0370511
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Reactive Oxygen Species)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.1.1.49 (Glucosephosphate Dehydrogenase)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Blood
MH  - COS Cells
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - *Cell Death/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Gene Expression
MH  - Glucosephosphate Dehydrogenase/antagonists & inhibitors/genetics/*metabolism
MH  - Hydrogen Peroxide/pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Oxidation-Reduction
MH  - PC12 Cells
MH  - Phosphorylation
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Transfection
EDAT- 1999/05/18 00:00
MHDA- 1999/05/18 00:01
CRDT- 1999/05/18 00:00
PHST- 1999/05/18 00:00 [pubmed]
PHST- 1999/05/18 00:01 [medline]
PHST- 1999/05/18 00:00 [entrez]
AID - 10.1152/ajpcell.1999.276.5.C1121 [doi]
PST - ppublish
SO  - Am J Physiol. 1999 May;276(5):C1121-31. doi: 10.1152/ajpcell.1999.276.5.C1121.