[Study on the influence of hypoxia induced microtubule damage on the opening of mitochondrial permeable transition pore of cardiac myocytes in rat].
OBJECTIVE
To investigate the influence of hypoxia induced microtubule damage on the opening of mitochondrial permeable transition pore (MPTP)of cardiac myocytes and on the decrease of respiratory function in rat.


METHODS
Primary cultured myocardial cells from 30 neonatal rats were randomized as normoxic group (A), hypoxia group (B), normoxia with microtubule destabilizing agent group (C, with treatment of 8 micromol/L colchicines for 30 minutes before normoxia), and hypoxia with microtubule stabilizing agent group (D, with treatment of 10 micromol/L taxol for 30 minutes before hypoxia). beta-tubulin immunofluorescence ,the opening of mitochondria permeability transition pore, and the mitochondrial inner membrane potential were detected at 0.5, 1, 3, 6 and 12 post-treatment hours (PTH), and the mitochondrial respiratory function was determined by MTT method. The changes in these indices were also determined in A group at the corresponding time-points.


RESULTS
Obvious damage of polymerized microtubule, opening of MPTP, mitochondrial inner membrane potential loss and decrease of myocardial respiratory activity were observed in both group B and C at 0.5 PTH, and they became more and more serious afterwards. However, the changes in the above indices in D group were much better than those in B group (P < 0.05 or 0.01), and no difference was found between D (92.8 +/- 4.0)% and C [(100.0 +/- 0.0) %, P > 0.05] groups.


CONCLUSIONS
Hypoxia played a role in the myocardial microtubule damage as well as in the opening of MPTP. Moreover, hypoxia could also impair the mitochondrial respiratory function. Microtubule destabilizing agent could reproduce well the process of hypoxia induced microtubule damage, while the stabilizing agent exerted protective effect by improving the transition of mitochondrial permeability and the mitochondria respiratory function.
Zheng
Ji
J
Institute of Burn Research, Southwest Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, The Third Military Medical University, Chongqing 400038, PR China.
Fang
Ya-dong
YD
Teng
Miao
M
Dang
Yong-ming
YM
Kuang
Yong
Y
Yan
Hong
H
Zhang
Dong-xia
DX
Song
Hua-pei
HP
Zhang
Qiong
Q
Huang
Yue-sheng
YS
D000818:Animals; D015687:Cell Hypoxia; D002478:Cells, Cultured; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial; D008870:Microtubules / Q000473:pathology*; D008929:Mitochondria, Heart / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley