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

Nephrology Dialysis Transplantation

Volumn 23, Issue 3, 2008, Pages 890-895

  Calò, Lorenzo A ^a   Davis, Paul A ^b   Pagnin, Elisa ^a   Bertipaglia, Lara ^a   Naso, Agostino ^a   Piccoli, Antonio ^a   Corradini, Robert ^c   Spinello, Michela ^c   Savica, Vincenzo ^c   Libera, Luciano Dalla ^a  

^a UNIVERSITY OF PADOVA   (Italy)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c Nephrology and Dialysis Units of Bolzano ^*  (Italy)

Author keywords

Anaemia; Apoptosis; Carnitine; Dialysis; Erythropoietin; Haem oxygenase 1

Indexed keywords

ANTIOXIDANT; CARNITINE; ERYTHROPOIETIN; HEME OXYGENASE 1; HEMOGLOBIN; PROTEIN BCL 2; MONOCROTALINE; PROTEIN KINASE B;

ANIMAL EXPERIMENT; APOPTOSIS; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; ENZYME INDUCTION; ERYTHROPOIESIS; GASTROCNEMIUS MUSCLE; HEART FAILURE; HEMATOCRIT; HEMODIALYSIS; HEMODIALYSIS PATIENT; HUMAN; HUMAN CELL; MALE; MONONUCLEAR CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; SIGNAL TRANSDUCTION; WESTERN BLOTTING; ANIMAL; CHEMICALLY INDUCED DISORDER; COMPARATIVE STUDY; DISEASE MODEL; DRUG EFFECT; METABOLISM; PATHOLOGY; PHYSIOLOGY; RENAL REPLACEMENT THERAPY; SKELETAL MUSCLE;

ANIMALS; APOPTOSIS; CARNITINE; DISEASE MODELS, ANIMAL; ERYTHROPOIESIS; ERYTHROPOIETIN; HEART FAILURE; HEMATOCRIT; HEME OXYGENASE-1; HEMOGLOBINS; HUMANS; LEUKOCYTES, MONONUCLEAR; MALE; MONOCROTALINE; MUSCLE, SKELETAL; PROTO-ONCOGENE PROTEINS C-AKT; PROTO-ONCOGENE PROTEINS C-BCL-2; RATS; RENAL DIALYSIS; SIGNAL TRANSDUCTION;

EID: 42449098584     PISSN: 09310509     EISSN: 14602385     Source Type: Journal    
DOI: 10.1093/ndt/gfm707     Document Type: Article

References (35)

1. Locatelli F, Aljama P, Barany P et al. European Best Practice Guidelines Working Group. Revised European best practice guidelines for the management of anaemia in patients with chronic renal failure. Nephrol Dial Transplant 2004; 19: 1-47
2. Smrzova J, Balla J, Barany P. Inflammation and resistance to erythropoiesis-stimulating agents - what do we know and what needs to be clarified? Nephrol Dial Transplant 2005; 20: 2-7
3. Drueke T. Hyporesponsiveness to recombinant human erythropoietin. Nephrol Dial Transplant 2001; 16: 25-28
4. Cheung JY, Miller BA. Molecular mechanisms of erythropoietin signaling. Nephron 2001; 87: 215-222
5. Bahlmann FH, Song R, Boehm SM et al. Low-dose therapy with the long-acting erythropoietin analogue darbepoetin alpha persistently activates endothelial Akt and attenuates progressive organ failure. Circulation 2004; 110: 1006-1012
6. Chong ZZ, Kang JQ, Maiese K. Erythropoietin is a novel vascular protectant through activation of Akt1 and mitochondrial modulation of cysteine proteases. Circulation 2002; 106: 2973-2979
7. Hurot JM, Cucherat M, Haugh M et al. Effects of L-carnitine supplementation in maintenance hemodialysis patients: a systematic review. J Am Soc Nephrol 2002; 13: 708-714
8. Savica V, Calvani M, Benatti P et al. Newer aspects of carnitine metabolism in uremia. Semin Nephrol. 2006; 26: 52-55
9. Peluso G, Barbarisi A, Savica V et al. Carnitine: an osmolyte that plays a metabolic role. J Cell Biochem 2001; 80: 1-10
10. Kitamura Y, Satoh K, Satoh T et al. Effect of L-carnitine on erythroid colony formation in mouse bone marrow cells. Nephrol Dial Transplant 2005; 20: 981-984
11. Cal̀o LA, Davis PA, Semplicini A et al. L-carnitine and erythropoiesis: relationship with heme oxygenase-1. Nephrol Dial Transplant 2005; 20: 1769-1770
12. Calo LA, Davis PA, Piccoli A et al. A role for heme oxygenase-1 in the antioxidant and antiapoptotic effects of erythropoietin: the start of a good news/bad news story? Nephron Physiol 2006; 103: 107-111
13. Davis PA, Calo LA. Carnitine's protective effect on oxidative stress is mediated by heme oxygenase-1. Nephrology 2006; 11: 569
14. Reznick AZ, Kagan VE, Ramsey R et al. Antiradical effects in l propionyl carnitine protection of the heart against ischemia-reperfusion injury: the possible role of iron chelation. Arch Biochem Biophys 1992; 296: 394-401
15. Sener G, Paskaloglu K, Saturoglu H et al. L-Carnitine ameliorates oxidative damage due to chronic renal failure in rats. J Cardiovasc Pharmacol 2004; 43: 698-705
16. Vescovo G, Ravara B, Gobbo Vet al. L-Carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure. Am J Physiol Cell Physiol 2002; 283: C802-C810
17. Boonsanit D, Kanchanapangka S, Buranakarl C. L-Carnitine ameliorates doxorubicin-induced nephrotic syndrome in rats. Nephrology 2006; 11: 313-320
18. Kopple JD, Ding H, Letoha A et al. L-Carnitine ameliorates gentamicin-induced renal injury in rats. Nephrol Dial Transplant 2002; 17: 2122-2131
19. Calo LA, Pagnin E, Davis PA et al. Antioxidant effect of L-carnitine and its short chain esters: relevance for the protection from oxidative stress related cardiovascular damage. Int J Cardiol 2006; 107: 54-60
20. Martin D, Rojo AI, Salinas M et al. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem 2004; 279: 8919-8929
21. Vescovo G, Zennaro R, Sandri M et al. Apoptosis of skeletal muscle myofibers and interstitial cells in experimental heart failure. J Mol Cell Cardiol 1998; 30: 2449-2459
22. Stenvinkel P, Heimburger O, Lindholm B et al. Are there two types of malnutrition in chronic renal failure? Evidence for relationships between malnutrition, inflammation and atherosclerosis (MIA syndrome). Nephrol Dial Transplant 2000; 15: 953-960
23. Locatelli F, Canaud B, Eckardt K et al. Oxidative stress in endstage renal disease: an emerging threat to patient outcome. Nephrol Dial Transplant 2003; 18: 1272-1280
24. Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997; 37: 517-554
25. Pantopoulos K, Hentze MW. Rapid responses to oxidative stress mediated by iron regulatory protein. EMBO J 1995; 14: 2917-2924
26. Cairo G, Castrusini E, Minotti G et al. Superoxide and hydrogen peroxide-dependent inhibition of iron regulatory protein activity: a protective stratagem against oxidative injury. FASEB J 1996; 10: 1326-1335
27. Mutomba MC, Yuan H, Konyavko M et al. Regulation of the activity of caspases by L-carnitine and palmitoylcarnitine. FEBS Lett 2000; 478: 19-25
28. Ishii T, Shimpo Y, Matsuoka Y et al. Anti-apoptotic effect of acetyl-lcarnitine and I-carnitine in primary cultured neurons. Jpn J Pharmacol 2000; 83: 119-124
29. Calo LA, Stanic L, Davis PA et al. Effect of epoetin on HO-1 mRNA level and plasma antioxidants in hemodialysis patients. Int J Clin Pharmacol Ther 2003; 41: 187-192
30. Testa U. Apoptotic mechanisms in the control of erythropoiesis. Leukemia 2004; 18: 1176-1199
31. Skurk C, Izumiya Y, Maatz H et al. The FOXO3 - a transcription factor regulates cardiac myocyte size downstream of AKT signaling. J Biol Chem 2005; 280: 20814-20823
32. Sandri M, Sandri C, Gilbert A et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 2004; 117: 399-412
33. McKinnell IW, Rudnicki MA. Molecular mechanisms of muscle atrophy. Cell 2004; 119: 907-910
34. Calvani M, Reda E, Arrigoni-Martelli E. Regulation by carnitine of myocardial fatty acid and carbohydrate metabolism under normal and pathological conditions. Basic Res Cardiol 2000; 95: 75-83
35. Robey RB, Hay N. Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene 2006; 25: 4683-4696