Differential effects of neonatal endotoxemia on heart and kidney carnitine palmitoyl transferase I.
OBJECTIVE
The heart and kidney are both affected in sepsis-related multiple organ failure. Both utilize fatty acid substrates during the neonatal period, and impairment of oxidative metabolism during sepsis could lead to bioenergetic failure. The enzyme carnitine palmitoyl transferase I (CPT I) is important in the control of fat oxidation in the neonatal period. The aim of this study was to determine the effects of sepsis on neonatal cardiac and renal CPT I.


METHODS
Suckling rats received 300 microgram/kg lipopolysaccharide intraperitoneally. Mitochondria were isolated from the heart and kidney after 2 hours. CPT I and II activity were measured radiochemically. Protein levels of M- and L- isoforms of CPT I, both of which are present in heart, were determined by Western blotting.


RESULTS
CPT I activity was decreased significantly in the heart but not in the kidney by endotoxemia, whereas CPT II activity was the same in each organ. To investigate the mechanism of this decrease, we carried out Western blotting of the CPT I isoforms in heart mitochondria. Neither M- nor L- isoform was decreased in amount. To determine whether free-radical attack could directly inhibit CPT I activity, control heart mitochondria were incubated with free-radical generating systems. Although hydrogen peroxide had no effect on CPT I activity, the reactive oxygen species nitric oxide, superoxide, and peroxynitrite, all of which are generated in the heart during sepsis, significantly inhibited CPT I activity.


CONCLUSIONS
The activity of CPT I, a rate-controlling step of fat oxidation, is significantly impaired in heart but not in kidney during neonatal sepsis. This may be caused by direct attack by free radicals, suggesting that antioxidant strategies could be of use in preventing sepsis-related cardiac damage.
Fukumoto
Koji
K
London, England.
Pierro
Agostino
A
Spitz
Lewis
L
Eaton
Simon
S
D000818:Animals; D000831:Animals, Newborn; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D019446:Endotoxemia / Q000201:enzymology*; D007668:Kidney / Q000201:enzymology*; D008928:Mitochondria / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D009569:Nitric Oxide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000494:pharmacology
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002334:Carnitine O-Palmitoyltransferase