PMID- 16263807
OWN - NLM
STAT- MEDLINE
DCOM- 20060522
LR  - 20131121
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 290
IP  - 5
DP  - 2006 May
TI  - Cadmium inhibits both intrinsic and extrinsic apoptotic pathways in renal 
      mesangial cells.
PG  - F1074-82
AB  - Cadmium is a potent nephrotoxin that has been shown to induce apoptosis in some 
      cells but also to prevent it under certain circumstances. In several clinical 
      situations and experimental models of injury to the renal glomerulus, 
      pathological proliferation of mesangial cells is followed by resolution involving 
      mesangial cell apoptosis. We investigated the effects of Cd(2+) on rat mesangial 
      cells induced to undergo apoptosis through either the extrinsic receptor-mediated 
      pathway or the intrinsic mitochondrial-dependent pathway. Camptothecin initiated 
      the intrinsic pathway with activation of caspase-9 and caspase-dependent cleavage 
      of procaspase-3. Tumor necrosis factor-alpha (TNF-alpha) initiated caspase-8 
      activity and cleavage of pro-caspase-3 at the convergence point of the two 
      pathways. However, pro-caspase-8 levels were low, and caspase-9 was also 
      activated in response to TNF-alpha, characteristic of what have been termed type 
      II cells. With both TNF-alpha and camptothecin, concurrent exposure to 10 microM 
      CdCl(2) suppressed DNA laddering, nuclear condensation, and pro-caspase-3 
      cleavage. It also decreased activity of both caspase-8 and caspase-9, prevented 
      caspase-8-dependent cleavage of the proapoptotic factor Bid, and suppressed 
      release of cytochrome c from mitochondria. At this 10-microM concentration, 
      Cd(2+) was unique among a number of metal ions in preventing DNA fragmentation. 
      We conclude that Cd(2+) is anti-apoptotic in rat mesangial cells, acting by a 
      mechanism that may involve general caspase inhibition. This may have consequences 
      for the resolution of nephritis in situations of mesangial cell 
      hyperproliferation.
FAU - Gunawardana, C Geeth
AU  - Gunawardana CG
AD  - Dept. of Laboratory Medicine and Pathobiology, Medical Sciences Bldg. Rm. 6302, 
      Univ. of Toronto, 1 King's College Circle, Toronto, Ontario, Canada.
FAU - Martinez, Raul E
AU  - Martinez RE
FAU - Xiao, Weiqun
AU  - Xiao W
FAU - Templeton, Douglas M
AU  - Templeton DM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051101
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 00BH33GNGH (Cadmium)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Casp8 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cadmium/*toxicity
MH  - Caspase 3
MH  - Caspase 8
MH  - Caspases/metabolism
MH  - DNA Damage
MH  - Mesangial Cells/*drug effects/physiology
MH  - Nephritis/chemically induced/physiopathology
MH  - Rats
EDAT- 2005/11/03 09:00
MHDA- 2006/05/23 09:00
CRDT- 2005/11/03 09:00
PHST- 2005/11/03 09:00 [pubmed]
PHST- 2006/05/23 09:00 [medline]
PHST- 2005/11/03 09:00 [entrez]
AID - 00067.2005 [pii]
AID - 10.1152/ajprenal.00067.2005 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2006 May;290(5):F1074-82. doi: 
      10.1152/ajprenal.00067.2005. Epub 2005 Nov 1.