Bimoclomol elevates heat shock protein 70 and cytoprotects rat neonatal cardiomyocytes.
Bimoclomol is a new compound that improves cell survival under experimental stress conditions partly by increasing intracellular heat shock proteins (HSPs). HSPs, especially HSP70, play a cytoprotective role in the rat heart. Rat neonatal cardiomyocytes were used to determine the ability of bimoclomol to induce HSP70 and affect cell survival across a broad concentration range (0.01-100 microM). Bimoclomol significantly elevated HSP70 levels at concentrations ranging from 0.01 to 10 microM, depending on the time of exposure. Pretreatment with bimoclomol for 24 h significantly increased survival of cells. There was a significant correlation between the increased levels of HSP70 and the increase in cell survival as a result of the treatment with bimoclomol. In conclusion, bimoclomol improved cell survival in rat neonatal cardiomyocytes, in part, by increasing the levels of HSP70. This cytoprotection began at the relatively low concentration of 0.1 microM, which is a concentration that can be achieved clinically.
Polakowski
James S
JS
Department of Integrative Pharmacology, Abbott Laboratories, Abbott Park, IL, USA. jim.polakowski@abbott.com
Wegner
Craig D
CD
Cox
Bryan F
BF
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D007094:Imides / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats
D018840:HSP70 Heat-Shock Proteins; D007094:Imides; D020011:Protective Agents; D011725:Pyridines; C108730:bimoclomol