title: Cellular redistribution of inducible Hsp70 protein in the human and rabbit heart in response to the stress of chronic hypoxia: role of protein kinases,.
abstract: Many infants who undergo cardiac surgery have a congenital cyanotic defect where the heart is chronically perfused with hypoxemic blood. Infant hearts adapt to chronic hypoxemia by activation of intracellular protein kinase signal transduction pathways. However, the involvement of heat shock protein 70 in adaptation to chronic hypoxemia and its role in protein kinase signaling pathways is unknown. We determined expression of message and subcellular protein distribution for inducible (Hsp70i) and constitutive heat shock protein 70 (Hsc70) in chronically hypoxic and normoxic infant human and rabbit hearts and their relationship to protein kinases. In chronically hypoxic human and rabbit hearts message levels for Hsp70i were elevated 4- to 5-fold compared with normoxic hearts, Hsp70i protein was redistributed from the particulate to the cytosolic fraction. In normoxic infants Hsp70i protein was distributed almost equally between the cytosolic and particulate fractions. Hsc70 message and subcellular distribution of Hsc70 protein were unaffected by chronic hypoxia. We then determined if protein kinases influence Hsp70i protein subcellular distribution. In rabbit hearts SB203580 and chelerythrine reduced Hsp70i message levels, whereas SB203580, chelerythrine, and curcumin reversed the subcellular redistribution of Hsp70i protein caused by chronic hypoxia, with no effect in normoxic hearts, indicating regulation of Hsp70i message and subcellular distribution of Hsp70i protein in chronically hypoxic rabbit hearts is influenced by protein kinase C and mitogen-activated protein kinases, specifically p38 MAPK and JNK. We conclude the Hsp70 signal transduction pathway plays an important role in adaptation of infant human and rabbit hearts to chronic hypoxemia.
authors.affiliation: Division of Pediatric Surgery, Medical College of Wisconsin and Children's Hospital of Wisconsin, Milwaukee, Wisconsin 53226, USA.
authors.forename: Parvaneh
authors.initials: P
authors.lastname: Rafiee
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.forename: Kirkwood A
authors.initials: KA
authors.lastname: Pritchard
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ogawa
authors.forename: Annie L W
authors.initials: AL
authors.lastname: Eis
authors.forename: Richard A
authors.initials: RA
authors.lastname: Komorowski
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Fitzpatrick
authors.forename: James S
authors.initials: JS
authors.lastname: Tweddell
authors.forename: S Bert
authors.initials: SB
authors.lastname: Litwin
authors.forename: Kathleen
authors.initials: K
authors.lastname: Mussatto
authors.forename: Robert D
authors.initials: RD
authors.lastname: Jaquiss
authors.forename: John E
authors.initials: JE
authors.lastname: Baker
mesh_terms: D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D015153:Blotting, Western; D003474:Curcumin / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006321:Heart / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D006801:Humans; D000860:Hypoxia; D007093:Imidazoles / Q000494:pharmacology; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D007511:Ischemia; D020935:MAP Kinase Signaling System; D008297:Male; D008565:Membrane Proteins; D009206:Myocardium / Q000378:metabolism*; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D007093:Imidazoles; D008565:Membrane Proteins; D010617:Phenanthridines; D011725:Pyridines; D012333:RNA, Messenger; C016299:chelerythrine; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D011493:Protein Kinase C; D003474:Curcumin; C093642:SB 203580