High molecular weight FGF-2 promotes postconditioning-like cardioprotection linked to activation of protein kinase C isoforms, as well as Akt and p70 S6 kinases. [corrected].
Fibroblast growth factor 2 (FGF-2) is a multifunctional protein translated as high and low molecular weight isoforms (hi- and lo-FGF-2, respectively). Although the postconditioning cardioprotective effect of lo-FGF-2 (18 kDa) has been documented, hi-FGF-2 is less well studied. We used an isolated perfused rat heart model of ischemia-reperfusion to study the effects of postischemic (during reperfusion) administration of hi-FGF-2 on recovery of contractile function and tissue salvage, as indicated by decreased cytosolic cytochrome c levels. Compared with the vehicle-treated group, hi-FGF-2-treated hearts had significantly improved recovery of systolic pressure, developed pressure, rates of contraction and relaxation, and coronary flow, as well as decreased relative levels of cytosolic cytochrome c. The effects of hi-FGF-2 on functional recovery and cytosolic cytochrome c were indistinguishable from those induced by lo-FGF-2. Both hi- and lo-FGF-2 upregulated relative levels of phosphorylated (activated) Akt and p70 S6 kinase, and they both promoted translocation of alpha, epsilon, and zeta isoforms of protein kinase C (PKC) to the particulate fraction of reperfused hearts. The magnitude of the effect on PKCzeta and p70 S6 kinases, however, was significantly more potent in the hi-FGF-2 than in the lo-FGF-2 group. We conclude that acute postischemic cardioprotection by hi- or lo-FGF-2 is isoform nonspecific and likely to be mediated by PKC and Akt. Nevertheless, isoform-specific functions are suggested by the augmented sensitivity of p70 S6 and PKCzeta to hi-FGF-2.
Jiang
Zhi-Sheng
ZS
Institute of Cardiovascular Disease and Key Laboratory for Arteriosclerology of Hunan Province, Hengyang City, Hunan 421001, PR China.
Wen
Ge-Bo
GB
Tang
Zhi-Han
ZH
Srisakuldee
Wattamon
W
Fandrich
Robert R
RR
Kardami
Elissavet
E
D000818:Animals; D015153:Blotting, Western; D002316:Cardiotonic Agents; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000494:pharmacology*; D006331:Heart Diseases / Q000517:prevention & control*; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D015428:Myocardial Reperfusion Injury / Q000473:pathology; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D002316:Cardiotonic Agents; D007527:Isoenzymes; D016222:Fibroblast Growth Factor 2; D051058:Oncogene Protein v-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D011493:Protein Kinase C