PMID- 15763427
OWN - NLM
STAT- MEDLINE
DCOM- 20050714
LR  - 20131121
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 17
IP  - 7
DP  - 2005 Jul
TI  - Effect of methylglyoxal on intracellular calcium levels and viability in renal 
      tubular cells.
PG  - 847-55
AB  - Methylglyoxal (2-oxopropanal), a physiological glucose metabolite, is a highly 
      reactive dicarbonyl compound that can induce stress in cells and cause apoptotic 
      cell death. This study examines the early signaling effects of methylglyxal on 
      renal cells. It was found that methylglyoxal caused a slow and sustained rise of 
      intracellular Ca2+ concentration ([Ca2+]i) in a concentration-dependent manner 
      (EC50=1.8 mM). Methylglyoxal also induced a [Ca2+]i rise when extracellular Ca2+ 
      was removed, but the magnitude was reduced by 80%. Depletion of intracellular 
      Ca2+ stores with thapsigargin (TG), an endoplasmic reticulum (ER) Ca2+ pump 
      inhibitor, did not affect methylglyoxal's effect. In Ca2+-free medium, the 
      methylglyoxal-induced [Ca2+]i rise was abolished by depleting stored Ca2+ with 
      carbonylcyanide m-chlorophenylhydrazone (CCCP; a mitochondrial uncoupler). 
      Methylglyoxal-caused [Ca2+]i rise in the Ca2+-containing medium was not affected 
      by modulation of protein kinase C activity, presence of voltage-gated Ca2+ 
      channel blockers, or preincubation with thiol-containing antioxidants. U73122, an 
      inhibitor of phospholipase C, abolished ATP (but not methylglyoxal)-induced 
      [Ca2+]i rise. Furthermore, the [Ca2+]i-elevating effect of methylglyoxal was cell 
      type-dependent, because methylglyoxal failed to cause [Ca2+]i rises in CHO-K1, 
      neutrophils, or platelets. Pretreatment with methylglyoxal for 0-24 h decreased 
      cell viability in a concentration- and time-dependent manner. Meanwhile, 
      methylglyoxal-induced cell death involved apoptotic and necrotic events, the 
      former being the dominant. These findings suggest that methylglyoxal induced a 
      significant rise in [Ca2+]i in Madin-Darby canine kidney (MDCK) renal tubular 
      cells by stimulating both extracellular Ca2+ influx and CCCP-sensitive 
      intracellular Ca2+ release via as yet unidentified mechanisms. The cell 
      type-specific Ca2+ signaling may play an important role in the early process of 
      cytotoxic action of methylglyoxal.
FAU - Jan, Chung-Ren
AU  - Jan CR
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung 813, Taiwan.
FAU - Chen, Ching-Hsein
AU  - Chen CH
FAU - Wang, Shu-Ching
AU  - Wang SC
FAU - Kuo, Soong-Yu
AU  - Kuo SY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20041208
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Fluorescent Dyes)
RN  - 722KLD7415 (Pyruvaldehyde)
RN  - EC 3.1.4.- (Type C Phospholipases)
RN  - SY7Q814VUP (Calcium)
RN  - TSN3DL106G (Fura-2)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - CHO Cells
MH  - Calcium/*metabolism
MH  - Calcium Signaling
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cricetinae
MH  - Cricetulus
MH  - Dogs
MH  - Dose-Response Relationship, Drug
MH  - Fluorescent Dyes
MH  - Fura-2
MH  - Humans
MH  - Intracellular Fluid/metabolism
MH  - Kidney Tubules/*cytology/metabolism
MH  - Necrosis
MH  - Neutrophils/drug effects/metabolism
MH  - Pyruvaldehyde/*metabolism/toxicity
MH  - Rabbits
MH  - Signal Transduction
MH  - Time Factors
MH  - Type C Phospholipases/physiology
EDAT- 2005/03/15 09:00
MHDA- 2005/07/15 09:00
CRDT- 2005/03/15 09:00
PHST- 2004/07/20 00:00 [received]
PHST- 2004/11/03 00:00 [revised]
PHST- 2004/11/03 00:00 [accepted]
PHST- 2005/03/15 09:00 [pubmed]
PHST- 2005/07/15 09:00 [medline]
PHST- 2005/03/15 09:00 [entrez]
AID - S0898-6568(04)00246-3 [pii]
AID - 10.1016/j.cellsig.2004.11.007 [doi]
PST - ppublish
SO  - Cell Signal. 2005 Jul;17(7):847-55. doi: 10.1016/j.cellsig.2004.11.007. Epub 2004 
      Dec 8.