PMID- 24280624
OWN - NLM
STAT- MEDLINE
DCOM- 20140814
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 32
IP  - 5
DP  - 2013
TI  - Cannabinoid receptor 2 expression in human proximal tubule cells is regulated by 
      albumin independent of ERK1/2 signaling.
PG  - 1309-19
LID - 10.1159/000354529 [doi]
AB  - BACKGROUND: The cannabinoid receptor type 2 (CB2) is reduced in podocytes of 
      animals and humans with Type 2 Diabetes Mellitus (T2DM), with activation of CB2 
      ameliorating albuminuria in animals. As albuminuria also is due to proximal 
      tubule dysfunction, the aim of this study is to investigate tubular expression of 
      CB2 under diabetic conditions in addition to the cell signaling pathways that 
      underlie these changes. METHODS: We characterized total CB2 protein in diabetic 
      animals and in Human Kidney 2 (HK2) cells exposed to elevated albumin and 
      glucose, the levels of CB2 mRNA and protein. We also used latrunculin to 
      determine if internalization of albumin was required to regulate CB2 levels. 
      Finally, we characterized the levels of active and total AKT, ERK1/2 and p38 in 
      response to albumin. RESULTS: There were no changes to CB2 expression in kidney 
      lysate from diabetic rats. In HK2 cells, expression of CB2 was unaltered 
      following exposure to high glucose. High albumin treatment alone and in 
      combination with high glucose, resulted in a significant reduction in CB2 
      receptor mRNA expression at 6 and 18 hours. CB2 protein expression was reduced at 
      6 and 24 hours, in high albumin and in combination with high glucose. 
      Internalization of albumin was required to regulate CB2 levels, and inhibition of 
      ERK1/2, did not rescue the loss of CB2 in response to albumin. CONCLUSION: We 
      have demonstrated that internalization of albumin is required to reduce CB2 mRNA 
      and protein expression in proximal tubules in vitro. Consequently, altered 
      expression of CB2 in both the podocytes and tubules may contribute to the 
      albuminuria observed in T2DM.
CI  - (c) 2013 S. Karger AG, Basel.
FAU - Jenkin, Kayte A
AU  - Jenkin KA
AD  - Biomedical and Lifestyle Diseases Unit, Victoria University, College of 
      Biomedical and Health Sciences, The University of Melbourne, Melbourne, 
      Australia.
FAU - McAinch, Andrew J
AU  - McAinch AJ
FAU - Briffa, Jessica F
AU  - Briffa JF
FAU - Zhang, Yuan
AU  - Zhang Y
FAU - Kelly, Darren J
AU  - Kelly DJ
FAU - Pollock, Carol A
AU  - Pollock CA
FAU - Poronnik, Philip
AU  - Poronnik P
FAU - Hryciw, Deanne H
AU  - Hryciw DH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131122
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Albumins)
RN  - 0 (Cnr2 protein, rat)
RN  - 0 (Receptor, Cannabinoid, CB2)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Albumins/*metabolism/pharmacokinetics
MH  - Animals
MH  - Cell Line
MH  - Diabetes Mellitus, Experimental/metabolism
MH  - Glucose/metabolism
MH  - Humans
MH  - Kidney Tubules, Proximal/cytology/*metabolism
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - Male
MH  - Podocytes/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, Cannabinoid, CB2/genetics/*metabolism
MH  - Signal Transduction/drug effects
EDAT- 2013/11/28 06:00
MHDA- 2014/08/15 06:00
CRDT- 2013/11/28 06:00
PHST- 2013/09/26 00:00 [accepted]
PHST- 2013/11/28 06:00 [entrez]
PHST- 2013/11/28 06:00 [pubmed]
PHST- 2014/08/15 06:00 [medline]
AID - 000354529 [pii]
AID - 10.1159/000354529 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2013;32(5):1309-19. doi: 10.1159/000354529. Epub 2013 Nov 
      22.