title: Correction of aberrant NADPH oxidase activity in blood-derived mononuclear cells from type II diabetes mellitus patients by a naturally fermented papaya preparation.
abstract: Supplementation of standardized fermented papaya preparation (FPP) to adult diabetic mice improves dermal wound healing outcomes. Peripheral blood mononuclear cells (PBMC) from type II diabetes mellitus (T2DM) patients elicit a compromised respiratory burst activity resulting in increased risk of infections for the diabetic patients.
  
  
  OBJECTIVE
  The objectives of the current study were to determine the effect of FPP supplementation on human diabetic PBMC respiratory burst activity and to understand underlying mechanisms of such action of FPP.
  
  
  RESULTS
  When stimulated with phorbol 12-myristate 13-acetate, the production of reactive oxygen species by T2DM PBMC was markedly compromised compared to that of the PBMC from non-DM donors. FPP treated ex vivo improved respiratory burst outcomes in T2DM PBMC. FPP treatment significantly increased phosphorylation of the p47phox subunit of NADPH oxidase. In addition, the protein and mRNA expression of Rac2 was potently upregulated after FPP supplemention. The proximal human Rac2 gene promoter is G-C rich and contains consensus binding sites for Sp1 and AP-1. While FPP had no significant effect on the AP-1 DNA binding activity, the Sp1 DNA binding activity was significantly upregulated in PBMC after treatment of the cells with FPP.
  
  
  METHODS
  This work provided first evidence that compromised respiratory burst performance of T2DM PBMC may be corrected by a nutritional supplement.
  
  
  CONCLUSIONS
  FPP can correct respiratory burst performance of T2DM PBMC via an Sp-1-dependant pathway. Studies testing the outcome of FPP supplementation in diabetic patients are warranted.
authors.affiliation: Department of Surgery, Comprehensive Wound Center, Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH 43210, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Dickerson
authors.forename: Bhakthi
authors.initials: B
authors.lastname: Deshpande
authors.forename: Urmila
authors.initials: U
authors.lastname: Gnyawali
authors.forename: Debbie
authors.initials: D
authors.lastname: Lynch
authors.forename: Gayle M
authors.initials: GM
authors.lastname: Gordillo
authors.forename: Dara
authors.initials: D
authors.lastname: Schuster
authors.forename: Kwame
authors.initials: K
authors.lastname: Osei
authors.forename: Sashwati
authors.initials: S
authors.lastname: Roy
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D029441:Carica / Q000737:chemistry*; D016022:Case-Control Studies; D002478:Cells, Cultured; D017322:Clinical Trials, Phase II as Topic; D015254:DNA Modification Methylases / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology*; D005260:Female; D005285:Fermentation; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D016897:Respiratory Burst / Q000187:drug effects; D016329:Sp1 Transcription Factor / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000097766:RAC2 GTP-Binding Protein
chemical_list: D000975:Antioxidants; D015254:DNA Modification Methylases; D019255:NADPH Oxidases; D010936:Plant Extracts; D021122:Protein Subunits; D016329:Sp1 Transcription Factor; D020744:rac GTP-Binding Proteins; D000097766:RAC2 GTP-Binding Protein; C060505:neutrophil cytosolic factor 1