title: Stem cell transplantation increases antioxidant effects in diabetic mice.
abstract: Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, blood glucose levels and insulin, and increased plasma adiponectin levels. The upregulation of HO-1 was associated with significantly (p<0.05) increased levels of peNOS and pAKT, but decreased levels of iNOS in the kidneys of db/db mice. Plasma creatinine levels also decreased (p<0.05), and the expression of type IV collagen was improved. Thus IBM-BMT+TT unregulated the expression of HO-1, peNOS and pAKT, while decreasing iNOS levels in the kidney of db/db mice. This was associated with an improvement in renal function.
authors.affiliation: Department of Stem Cell Disorders, Kansai Medical University, Moriguchi City, Osaka, Japan.
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Luca
authors.initials: L
authors.lastname: Vanella
authors.forename: Yuming
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: Takashi
authors.initials: T
authors.lastname: Takaki
authors.forename: Joseph I
authors.initials: JI
authors.lastname: Shapiro
authors.forename: Susumu
authors.initials: S
authors.lastname: Ikehara
mesh_terms: D055372:AMP-Activated Protein Kinases; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001786:Blood Glucose; D001835:Body Weight; D016026:Bone Marrow Transplantation; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008214:Lymphocytes / Q000502:physiology; D051379:Mice; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D033581:Stem Cell Transplantation; D013950:Thymus Gland / Q000473:pathology / Q000637:transplantation; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007328:Insulin; D019001:Nitric Oxide Synthase; D051547:Heme Oxygenase-1; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: HO-1; IBM-BMT+TT; antioxidant; diabetic nephropathy.