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Cellular redistribution of inducible Hsp70 protein in the human and rabbit heart in response to the stress of chronic hypoxia: role of protein kinases,. J Biol Chem 2003 Oct 31;278(44):43636-44

Date

08/26/2003

Pubmed ID

12937165

DOI

10.1074/jbc.M212993200

Scopus ID

2-s2.0-0242321893   48 Citations

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.

Author List

Rafiee P, Shi Y, Pritchard KA Jr, Ogawa H, Eis AL, Komorowski RA, Fitzpatrick CM, Tweddell JS, Litwin SB, Mussatto K, Jaquiss RD, Baker JE

Authors

John E. Baker PhD Professor in the Surgery department at Medical College of Wisconsin
Kathleen Mussatto in the CTSI department at Medical College of Wisconsin - CTSI
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Alkaloids
Animals
Benzophenanthridines
Blotting, Western
Curcumin
Electrophoresis, Polyacrylamide Gel
Enzyme Inhibitors
Female
HSC70 Heat-Shock Proteins
HSP70 Heat-Shock Proteins
Heart
Heme Oxygenase (Decyclizing)
Heme Oxygenase-1
Humans
Hypoxia
Imidazoles
Immunohistochemistry
Infant
Infant, Newborn
Ischemia
MAP Kinase Signaling System
Male
Membrane Proteins
Myocardium
Phenanthridines
Protein Kinase C
Pyridines
RNA, Messenger
Rabbits
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Time Factors
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a