PMID- 19019916
OWN - NLM
STAT- MEDLINE
DCOM- 20090330
LR  - 20171116
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 296
IP  - 2
DP  - 2009 Feb
TI  - Advanced oxidation protein products induce mesangial cell perturbation through 
      PKC-dependent activation of NADPH oxidase.
PG  - F427-37
LID - 10.1152/ajprenal.90536.2008 [doi]
AB  - Mesangial deposition of extracellular matrix (ECM) is a hallmark of several 
      glomerular diseases including diabetic nephropathy. Accumulation of advanced 
      oxidation protein products (AOPPs) has been found in diabetes and chronic kidney 
      disease and linked to mesangial ECM deposition and progressive glomerulosclerosis 
      in these disorders. Although emerging evidence implicates AOPPs as the renal 
      pathogenic factors, the underlying mechanisms have not been investigated. Here, 
      using cultured rat mesangial cells (MCs) as a model, we identify AOPPs as the 
      important mediators for activation of MC NADPH oxidase. Exposure of MCs to AOPPs, 
      through membrane-associated phosphorylation of PKCalpha, induced rapid 
      phosphorylation of cytosolic p47(phox) and its membrane translocation, enhanced 
      interaction of p47(phox) with the membrane components p22(phox) and Nox4, and 
      increased expression of these key regulatory subunits of NADPH oxidase. Challenge 
      with AOPPs triggered cytosolic superoxide generation, resulting in upregulation 
      of fibronectin and collagen IV genes and proteins and overexpression of TGF-beta1 
      via a PKC-NADPH oxidase-dependent pathway, as these downstream events were 
      blocked by the inhibitors of PKC, inhibitors of NADPH oxidase, or the cytosolic 
      superoxide scavenger. These data provide new information for understanding the 
      molecular basis underlying AOPP-induced MC perturbation and might be a central 
      step toward development of new interventions.
FAU - Wei, Xiao Fan
AU  - Wei XF
AD  - Div. of Nephrology, Nanfang Hospital, 1838 North Guangzhou Ave., Guangzhou 
      510515, China.
FAU - Zhou, Qiu Gen
AU  - Zhou QG
FAU - Hou, Fan Fan
AU  - Hou FF
FAU - Liu, Bei Yi
AU  - Liu BY
FAU - Liang, Min
AU  - Liang M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20081119
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Collagen Type IV)
RN  - 0 (Fibronectins)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 11062-77-4 (Superoxides)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Collagen Type IV/metabolism
MH  - Cytosol/metabolism
MH  - Enzyme Activation
MH  - Extracellular Matrix/metabolism
MH  - Fibronectins/metabolism
MH  - Mesangial Cells/*enzymology
MH  - NADPH Oxidases/*metabolism
MH  - *Oxidative Stress
MH  - Phosphorylation
MH  - Protein Kinase C/*metabolism
MH  - Rats
MH  - Superoxides/metabolism
MH  - Transforming Growth Factor beta1/immunology/metabolism
MH  - Up-Regulation
EDAT- 2008/11/21 09:00
MHDA- 2009/03/31 09:00
CRDT- 2008/11/21 09:00
PHST- 2008/11/21 09:00 [pubmed]
PHST- 2009/03/31 09:00 [medline]
PHST- 2008/11/21 09:00 [entrez]
AID - 90536.2008 [pii]
AID - 10.1152/ajprenal.90536.2008 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2009 Feb;296(2):F427-37. doi: 
      10.1152/ajprenal.90536.2008. Epub 2008 Nov 19.