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Sheng Li Xue Bao. 2017 Aug 25;69(4):367-377.

Activation of caspase-12 at early stage contributes to cardiomyocyte apoptosis in trauma-induced secondary cardiac injury.

Author information

1
Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
2
State Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan 030001, China.
3
Department of Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, China.
4
Intensive Care Unit, Blacktown Hospital, Blacktown NSW 2148, Australia.
5
Cardiothoracic Surgery, General Hospital of Taiyuan Iron and Steel Co. Affiliated to Shanxi Medical University, Taiyuan 030003, China.
6
Department of Pharmacology, Shanxi Medical University, Taiyuan 030001, China.
7
Cardiothoracic Surgery, General Hospital of Taiyuan Iron and Steel Co. Affiliated to Shanxi Medical University, Taiyuan 030003, China. lf1207@126.com.

Abstract

Trauma-induced secondary cardiac injury (TISCI) is associated with increased adverse cardiac events and death. We have previously reported that TISCI results in myocardial apoptosis and secondary cardiac dysfunction. However, the underlying mechanism is unclear. To identify the time course of trauma-induced cardiomyocyte apoptosis and possible apoptotic pathway, traumatic rat models were built with Noble-Collip drum. Meanwhile, normal rat cardiomyocytes were cultured with traumatic plasma (TP) for 48 h. Cardiomyocyte apoptosis, cardiac function and the apoptosis related enzymes, including caspase-3, -8, -9, and -12, were determined. The results showed that there was no direct injury of rat hearts immediately after trauma. However, compared with hearts from the sham rats, hearts isolated from traumatic rats exhibited reduced +dP/dTmax and -dP/dTmax 24 h after trauma. In traumatic rats, myocardial apoptotic index and caspase-3 activity obviously increased 6 h after trauma, and achieved the maximal value 12 h after trauma. The activity and expression of caspase-12, an endoplasmic reticulum (ER) stress-specific caspase, elevated markedly 3 h after trauma and reached its peak 6 h after trauma. Otherwise, caspase-8 (extrinsic apoptotic pathway) and caspase-9 (intrinsic apoptotic pathway) in the myocardial tissue of traumatic rats were activated 24 h after trauma. Meanwhile, incubation of normal rat cardiomyocytes with TP increased caspase-12 activity at 6 h, caspase-3 activity at 12 h, caspase-8 and -9 activities at 24 h, respectively. TP-induced cardiomyocyte apoptosis was virtually abolished by Z-ATAD-FMK (a caspase-12 specific inhibitor). In addition, there was a significant negative correlation between myocardial caspase-12 activity and trauma-induced secondary cardiac dysfunction. Our present study demonstrated that caspase-12 is firstly activated and plays an important role in TISCI rats. Inhibition of caspase-12 mediated apoptosis may be a novel strategy in ameliorating posttraumatic cardiomyocyte apoptosis and secondary cardiac injury.

PMID:
28825094
[Indexed for MEDLINE]
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