Effect of dl-praeruptorin A on desmin and vimentin content in rat ischemia/reperfusion myocardiocytes.
BACKGROUND
Intermediate filament (IF) proteins have been thought to play a role in nuclear centration, organelle movement and maintenance of cell shape. dl-praeruptorin A (Pd-Ia), a novel Ca2+-influx blocker and K+-channel opener isolated from Chinese traditional herbal medicine Qian-Hu, has been demonstrated to inhibit expression of apoptosis related proteins and reduce the level of proinflammatory factors in ischemia/reperfusion myocardiocytes. Morphologically, whether Pd-Ia effects myocardiocyte IFs remains unclear. The purpose of this study was, for the first time, to evaluate the in vivo effects of Pd-Ia on IF desmin and vimentin content in order to further explore its cardioprotection against ischemia and elucidate its mechanism of action.


METHODS
Rats underwent a 30 minutes coronary occlusion followed by 120 minutes reperfusion. Assessment of desmin and vimentin content of myocardiocytes was performed by immunohistochemistry, Western blot, Hematoxylin-Eosin staining and densitometry.


RESULTS
Pretreatment with i.v. infusion of Pd-Ia prior to ischemia significantly increased desmin and vimentin content and alleviated defects caused by the ischemia/reperfusion insult, e.g. with Pd-Ia at a dose of 0.5 or 1.0 mg/kg, integrated density values of desmin were increased from 61 478 +/- 10 074 to 177 408 +/- 10 395 and 195 784 +/- 20 057, and vimentin from 59 189 +/- 19 853 to 164 781 +/- 19 543 and 185 696 +/- 20 957 (P < 0.01, vs placebo), respectively. The recovery of desmin seemed to be stronger and appeared earlier than that of vimentin.


CONCLUSIONS
Pd-Ia protectively increased IF desmin and vimentin content in ischemia/reperfusion myocardiocytes, which might be partially responsible for its cardioprotection against ischemia.
Chang
He
H
Division of Cardiology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-dori, Niigata 951-8510, Japan.
Chu
Xiao-yu
XY
Zou
Jun
J
Chang
Tian-hui
TH
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D003374:Coumarins / Q000494:pharmacology*; D003893:Desmin / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014746:Vimentin / Q000032:analysis*
D003374:Coumarins; D003893:Desmin; D004365:Drugs, Chinese Herbal; D014746:Vimentin; C441070:praeruptorin A; D002118:Calcium