Related Experiment Video
Updated: Jun 25, 2026
Isolation of Atrial Cardiomyocytes from a Rat Model of Metabolic Syndrome-related Heart Failure with Preserved Ejection Fraction
Published on: July 26, 2018
PAF exerts a direct apoptotic effect on the rat H9c2 cardiomyocytes in Ca2+-dependent manner
Dan Zhao1, Wen-Feng Chu, Ling Wu
1Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, and The Second Affiliated Hospital, Harbin, People's Republic of China.
Background:
Previous studies suggested that platelet-activating factor (PAF) plays an important role in ischemic diseases. Apoptosis has been implicated in myocardial infarction-related cell death. The present study was designed to determine whether PAF could induce apoptosis in cardiac myocytes and the underlying mechanisms by which PAF causes apoptosis.
Methods:
H9c2 cardiac myocytes were used to investigate the effect of PAF on intracellular calcium concentration, cell viability and cell apoptosis. Signaling pathway of caspase-3, cytochrome c and MAPK (ERK, JNK, p38) was determined during the PAF induced apoptosis.
Results:
First, our results showed that treatment of H9c2 cardiomyocytes with PAF (0.2 to 20 microM) caused apoptosis in these cells and the apoptotic process was suppressed by either BN52021 (an antagonist of PAF receptor) or BAPTA/AM (an intracellular Ca2+ chelator), suggesting an involvement of PAF and its receptor mediated calcium-dependent signaling. Second, we found that activity of p38-MAPK (mitogen-activated protein kinase) and caspase-3 was elevated in the cells treated with PAF, without altering activity of ERK and JNK, and that PAF-induced enhancement of caspase-3 activity was attenuated by application of either BAPTA/AM or SB203580 (p38 inhibitor). Furthermore, PAF-induced apoptosis and release of cytochrome c from mitochondria was blunted by SB203580, and PAF-induced enhancement of p38 activity was also attenuated by BAPTA/AM.
Conclusion:
Our data implicate that a PAF and its receptor in triggering apoptosis occurs in cultured H9c2 cardiac myocytes via a calcium-dependent p38 MAPK activated cytochrome c/caspase-3 apoptosis signaling pathway.
Insights
Platelet-activating factor (PAF) induces apoptosis in cardiac myocytes through a calcium-dependent pathway involving p38 MAPK and caspase-3. This finding is crucial for understanding myocardial infarction and developing targeted therapies.
Area of Science:
- Cardiovascular Research
- Cell Biology
- Molecular Medicine
Background:
- Platelet-activating factor (PAF) is implicated in ischemic diseases.
- Apoptosis is a key mechanism in myocardial infarction-related cell death.
Purpose of the Study:
- To determine if PAF induces apoptosis in cardiac myocytes.
- To elucidate the underlying mechanisms of PAF-induced apoptosis.
Main Methods:
- H9c2 cardiac myocytes were treated with PAF to assess apoptosis, intracellular calcium, and signaling pathways.
- Key pathways analyzed included caspase-3, cytochrome c, and MAPK (ERK, JNK, p38).
Main Results:
- PAF induced apoptosis in H9c2 cells, suppressed by PAF receptor antagonist and calcium chelator.
- PAF elevated p38-MAPK and caspase-3 activity, but not ERK or JNK.
- Apoptosis and cytochrome c release were linked to calcium-dependent p38 MAPK activation of caspase-3.
Conclusions:
- PAF triggers apoptosis in cardiac myocytes via a calcium-dependent p38 MAPK signaling pathway.
- This pathway involves the activation of cytochrome c and caspase-3.
- Findings provide insights into PAF's role in cardiac cell death mechanisms.
