Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FGF-16 has been reported to be preferentially expressed in the adult rat heart. We have investigated the expression of FGF-16 in the perinatal and postnatal heart and its functional significance in neonatal rat cardiac myocytes. FGF-16 mRNA accumulation was observed by quantitative RT-PCR between neonatal days 1 and 7, with this increased expression persisting into adulthood. FGF-2 has been shown to increase neonatal rat cardiac myocyte proliferative potential via PKC activation. Gene array analysis revealed that FGF-16 inhibited the upregulation by FGF-2 of cell cycle promoting genes including cyclin F and Ki67. Furthermore, the CDK4/6 inhibitor gene Arf/INK4A was upregulated with the combination of FGF-16 and FGF-2 but not with either factor on its own. The effect on Ki67 was validated by protein immunodetection, which also showed that FGF-16 significantly decreased FGF-2-induced Ki67 labeling of cardiac myocytes, although it alone had no effect on Ki67 labeling. Inhibition of p38 MAPK potentiated cardiac myocyte proliferation induced by FGF-2 but did not alter the inhibitory action of FGF-16. Receptor binding assay showed that FGF-16 can compete with FGF-2 for binding sites including FGF receptor 1. FGF-16 had no effect on activated p38, ERK1/2, or JNK/SAPK after FGF-2 treatment. However, FGF-16 inhibited PKC-alpha and PKC-epsilon activation induced by FGF-2 and, importantly, IGF-1. Collectively, these data suggest that expression and release of FGF-16 in the neonatal myocardium interfere with cardiac myocyte proliferative potential by altering the local signaling environment via modulation of PKC activation and cell cycle-related gene expression.
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PMID:FGF-16 is released from neonatal cardiac myocytes and alters growth-related signaling: a possible role in postnatal development. 1833 64

The anti-cancer drug doxorubicin is associated with an increased risk of cardiac damage and dysfunction, which can be acute as well as chronic. Fibroblast growth factor 2 (FGF-2) provides cardioprotection from ischemia-reperfusion injury but its effects on doxorubicin-induced damage are not known. We investigated the acute effects of doxorubicin administered in the absence and presence of FGF-2 pre-treatment, on isolated mouse perfused heart function over a period of 120 min. Doxorubicin elicited a significant decrease in left ventricular developed pressure (DP) at 30 min that persisted throughout the study. No effect on lactate dehydrogenase levels was detected in the perfusate, suggesting a lack of significant plasma membrane damage. FGF-2 pre-treatment lessened the deleterious effect of doxorubicin on DP significantly, and this beneficial effect of FGF-2 was blunted by protein kinase C inhibition with chelerythrine. Pre-treatment with a non-mitogenic FGF-2 mutant or FGF-16 also protected against a doxorubicin-induced decrease in DP. FGF-16 as well as FGF-2 pre-treatment elicited a small and transient negative inotropic effect. In conclusion, FGF-2 and FGF-16 increase resistance to acute doxorubicin-induced cardiac dysfunction, and protein kinase C activation is implicated in this response.
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PMID:FGF-2 and FGF-16 protect isolated perfused mouse hearts from acute doxorubicin-induced contractile dysfunction. 2343 Mar 53