Balance between hypertrophic and hypoxic stimulus in caspase-3 activation during rat heart development.
During heart development, cell hyperplasia and hypertrophy are the main mechanisms by which cardiac mass grows. Both these processes along with programmed cell death lead to complete growth and function. In addition, since the establishment of cardiac function depends on the relationship between oxygen supply and demand, we investigated some of the molecular mechanisms at the basis of rat myocardial cell response to hypoxic stress at different times of neonatal life. In particular, the role played by hypertrophic and survival factors like NF-kB and IAP-1 (Inhibiting Apoptosis Protein) and by death factors ASK-1 (Apoptosis Signal Regulating Kinase), JNK/SAPK (Jun-N-Terminal-Kinase/Stress-Activated Protein Kinase) pathways in regulating caspase-3 expression and activity has been evaluated by immunohistochemical and Western blotting analyses, respectively. Level of phosphorylation of IkBalpha and IAP-1 expression were substantial in 8-day-old hypoxic hearts, suggesting the persistence of NF-kB driven hypertrophic signal along with a rescue attempt against hypoxic stress. In contrast, ASK-1 mediated JNK/SAPK activation, regulating Bcl(2) levels, allows Bax homodimerization and caspase-3 activation in the same experimental conditions. Thus, a regulation carried out by NF-kB and JNK/SAPK pathways on caspase-3 activation at day 8 of neonatal life can be suggested as the main factor for the heart 'adaptive' response to hypoxia.
Cataldi
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A
Dipartimento di Biomorfologia, Università G. D'Annunzio, Via dei Vestini 6, Chieti-Pescara 66100, Italy. cataldi@unich.it
Rapino
C
C
Bianchi
G
G
Centurione
L
L
Zingariello
M
M
Di Giulio
C
C
Antonucci
A
A
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D006332:Cardiomegaly / Q000473:pathology*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D048429:Cell Size; D004789:Enzyme Activation / Q000502:physiology*; D005260:Female; D006321:Heart / Q000254:growth & development*; D000860:Hypoxia / Q000473:pathology*; D020672:I-kappa B Proteins / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051034:Inhibitor of Apoptosis Proteins; D048848:MAP Kinase Kinase Kinase 5 / Q000502:physiology; D009206:Myocardium / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D011247:Pregnancy; D011506:Proteins / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000503:physiopathology; D016019:Survival Analysis
D020672:I-kappa B Proteins; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D011506:Proteins; D048848:MAP Kinase Kinase Kinase 5; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases