title: Additive effects of hypertension and diabetes on renal cortical expression of PKC-alpha and -epsilon and alpha-tubulin but not PKC-beta 1 and -beta 2.
abstract: OBJECTIVE
  This study examined the separate and combined effects of hypertension and diabetes on renal cortical expression of protein kinase C (PKC) isoforms -beta 1, -beta 2, -alpha and -epsilon, to determine whether albuminuria is the result of an increase in the expression of one or a combination of PKC isoforms. Corresponding changes in renal microtubules were also assessed.
  
  
  METHODS
  Diabetes (D) was induced in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) by streptozotocin. After 24 weeks, PKC expression was determined by Western blot and microtubules were assessed by immunohistochemistry for alpha-tubulin protein.
  
  
  RESULTS
  Diabetes was characterized by significant increases in glycated haemoglobin (HbA1c) as compared to controls (C). There was a significant increase of three- to four-fold in PKC protein content for all four isoforms in renal cortex from SHR-C and WKY-D, and similar and significant levels of albuminuria (approximately 10 mg/24 h) observed in these groups in comparison to WKY-C (approximately 1 mg/24 h). Interestingly, PKC-alpha and -epsilon but not PKC-beta 1 and -beta 2 protein content was doubled in SHR-D, and albuminuria increased tenfold (approximately 100 mg/24 h) in comparison to SHR-C and WKY-D. These changes were paralleled by a significant decrease in alpha-tubulin protein content of approximately 50% in SHR-C and approximately 33% in WKY-D compared to WKY-C, with a further decrease of approximately 67% in SHR-D compared to WKY-C.
  
  
  CONCLUSIONS
  These findings indicate that PKC expression can be increased by either diabetes or hypertension, and that there are further specific increases in the expression of PKC isoforms -alpha and -epsilon in the model of combined diabetes and hypertension. In addition, the degree of disruption in microtubular cytoskeleton appears to be correlated with PKC activation and levels of albuminuria.
authors.affiliation: Endocrine Unit, Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia. Tanya.Osicka@med.monash.edu.au
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Osicka
authors.forename: Leileata M
authors.initials: LM
authors.lastname: Russo
authors.forename: Mei-Lan
authors.initials: ML
authors.lastname: Qiu
authors.forename: Gail C
authors.initials: GC
authors.lastname: Brammar
authors.forename: Vicki
authors.initials: V
authors.lastname: Thallas
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Forbes
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Comper
authors.forename: George
authors.initials: G
authors.lastname: Jerums
mesh_terms: D000419:Albuminuria / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001794:Blood Pressure / Q000502:physiology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D007672:Kidney Cortex / Q000201:enzymology*; D008297:Male; D008955:Models, Cardiovascular; D011493:Protein Kinase C / Q000096:biosynthesis*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000502:physiology; D013599:Systole / Q000502:physiology; D014404:Tubulin / Q000096:biosynthesis*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D014404:Tubulin; C497257:Prkce protein, rat; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon