Carnitine-mediated improved response to erythropoietin involves induction of haem oxygenase-1:: studies in humans and in an animal model

被引：14

作者：

Calo, Lorenzo A. ^{[1
]}

Davis, Paul A. ^{[2
]}

Pagnin, Elisa ^{[1
]}

Bertipaglia, Lara ^{[1
]}

Naso, Agostino ^{[3
]}

Piccoli, Antonio ^{[4
]}

Corradini, Robert

Spinello, Michela

Savica, Vincenzo

Libera, Luciano Dalla ^{[5
]}

机构：

[1] Univ Padua, Dept Clin & Expt Med, Clin Med 4, I-35128 Padua, Italy

[2] Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA

[3] Univ Padua, Div Nephrol 2, I-35100 Padua, Italy

[4] Univ Padua, Div Nephrol 1, I-35100 Padua, Italy

[5] Univ Padua, CNR Unit Muscle Biol & Pathophysiol, Dept Biomed Sci, I-35100 Padua, Italy

来源：

NEPHROLOGY DIALYSIS TRANSPLANTATION | 2008年 / 23卷 / 03期

关键词：

anaemia; apoptosis; carnitine; dialysis; erythropoietin; haem oxygenase-1;

D O I：

10.1093/ndt/gfm707

中图分类号：

R3 [基础医学]; R4 [临床医学];

学科分类号：

1001 ; 1002 ; 100602 ;

摘要：

Background. Carnitine improves erythropoetin (EPO) response and anaemia in haemodialysis patients (HD); however, the mechanism(s) responsible remain unidentified. We have reported that carnitine induces haem oxygenase (HO)-1, which is an antioxidant and antiapoptotic that acts via pathways shared with EPO. Therefore carnitine's effect on these pathways may account for the improved EPO response. This study evaluates carnitine's effect on protein expression of HO-1 in unexplained EPO resistant HD. Carnitine's effect was assessed by HO-1 expression in patients and compared to its antiapoptotic effect via HO-1 induction in a rat model of carnitine-treated heart failure. Methods. Unexplained EPO resistant HD mononuclear cell HO-1 and rat gastrocnemious muscle HO-1 and Bcl-2 protein expression were evaluated by western blot. Results. HD's haemoglobin (Hb) and haematocrit (Ht) were not different before carnitine treatment: 8.8 +/- 0.4 mg/dl versus 8.98 +/- 0.13 and 30.20% +/- 0.84 versus 30.72 +/- 1.14, respectively. Carnitine increased HO-1, Hb and Ht compared with patients not treated with carnitine: 2.40 +/- 0.58 versus 1.49 +/- 0.41, P = 0.02; 11.22 +/- 0.54 versus 8.90 +/- 0.15, P < 0.0001; 32.72 +/- 1.77 versus 30.66 +/- 0.43, P = 0.035, respectively. Carnitine-treated HD's HO-1 significantly correlated with haemoglobin. HO-1 and Bcl-2 protein levels in untreated heart failure rat's gastrocnemious muscle were reduced when compared with controls: 3.41 +/- 0.49 versus 5.32 +/- 0.38 and 0.69 +/- 0.11 versus 1.65 +/- 0.37, respectively, but were higher in carnitine-treated heart failure rats: 4.8 +/- 0.32 versus 3.41 +/- 0.49, P < 0.0002 and 1.09 +/- 0.08 versus 0.69 +/- 0.11, P = 0.0007, respectively. Conclusions. These results are consistent with an involvement of HO-1 in carnitine's effect on erythropoiesis. The initial signals or effectors responsible for carnitine's effect remain to be identified.

引用

页码：890 / 895

页数：6

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