Functional significance of hemodynamic overload-induced expression of leukemia-inhibitory factor in the adult mammalian heart.
BACKGROUND
Leukemia-inhibitory factor (LIF) is a member of the interleukin-6 family of cytokines that utilize gp130 as a common signaling component. In the present study, we examined the mechanisms that govern LIF expression and functional effects in the adult heart.


RESULTS
LIF mRNA and protein biosynthesis were examined in the adult feline heart after hemodynamic overloading ex vivo. Both LIF mRNA and protein expression were detected within 60 to 90 minutes after hemodynamic overloading. Studies in isolated adult cardiac myocytes showed that these cells synthesized both LIF mRNA and protein. The functional effects of LIF in the heart were demonstrated by studies that showed that LIF stimulation led to a significant increase in general protein synthesis and an increase in sarcomeric protein synthesis. Pretreatment with LIF also protected the cells against hypoxia/reoxygenation-induced cardiac myocyte apoptosis and cellular injury. Finally, LIF had no effect on isolated cardiac myocyte cell motion.


CONCLUSIONS
Hemodynamic overload is a sufficient stimulus for LIF expression in the adult mammalian heart. Given that LIF confers both hypertrophic and cytoprotective responses in adult cardiac myocytes, this study suggests that the expression of LIF within the heart may play an important role in mediating homeostatic responses within the myocardium.
Winters Center for Heart Failure Research, Department of Medicine, Houston VA Medical Center,Baylor College of Medicine, Houston, TX 77030, USA.
F
F
Wang
Y
Y
Seta
G
G
Baumgarten
D J
DJ
Engel
N
N
Sivasubramanian
D L
DL
Mann
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015152:Blotting, Northern; D015153:Blotting, Western; D002415:Cats; D015687:Cell Hypoxia; D004268:DNA-Binding Proteins / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation; D006131:Growth Inhibitors / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D006439:Hemodynamics / Q000502:physiology; D066298:In Vitro Techniques; D015850:Interleukin-6; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011312:Pressure; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D005419:Flavonoids; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; D012333:RNA, Messenger; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D007770:L-Lactate Dehydrogenase; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one