Propofol inhibits parthanatos via ROS-ER-calcium-mitochondria signal pathway in vivo and vitro.

Abstract

Parthanatos is a new form of programmed cell death. It has been recognized to be critical in cerebral ischemia-reperfusion injury, and reactive oxygen species (ROS) can induce parthanatos. Recent studies found that propofol, a widely used intravenous anesthetic agent, has an inhibitory effect on ROS and has neuroprotective in many neurological diseases. However, the functional roles and mechanisms of propofol in parthanatos remain unclear. Here, we discovered that the ROS-ER-calcium-mitochondria signal pathway mediated parthanatos and the significance of propofol in parthanatos. Next, we found that ROS overproduction would cause endoplasmic reticulum (ER) calcium release, leading to mitochondria depolarization with the loss of mitochondrial membrane potential. Mitochondria depolarization caused mitochondria to release more ROS, which, in turn, contributed to parthanatos. Also, we found that propofol inhibited parthanatos through impeding ROS overproduction, calcium release from ER, and mitochondrial depolarization in parthanatos. Importantly, our results indicated that propofol protected cerebral ischemia-reperfusion via parthanatos suppression, amelioration of mitochondria, and ER swelling. Our findings provide new insights into the mechanisms of how ER and mitochondria contribute to parthanatos. Furthermore, our studies elucidated that propofol has a vital role in parthanatos prevention in vivo and in vitro, and propofol can be a promising therapeutic approach for nerve injury patients.

• Authors: Hanhui Zhong, Rui Song, Qiongni Pang, Yawei Liu, Jinling Zhuang, Yeming Chen, Jijie Hu, Jian Hu, Youtan Liu, Zhifeng Liu, Jing Tang
• Journal: Cell death & disease (Cell Death Dis) Vol. 9 Issue 10 Pg. 932 (09 17 2018) ISSN: 2041-4889 [Electronic] England
• PMID: 30224699 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Reactive Oxygen Species
• Adenosine Triphosphate
• Calcium
• Propofol

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Blotting, Western
• Brain Ischemia (drug therapy, metabolism)
• Calcium (metabolism)
• Cell Death (drug effects)
• Cell Line
• Endoplasmic Reticulum (drug effects, metabolism)
• Humans
• Infarction, Middle Cerebral Artery (drug therapy, metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mice, Inbred C57BL
• Microscopy, Electron, Transmission
• Mitochondria (drug effects, metabolism)
• Oxidative Stress (drug effects)
• Propofol (therapeutic use)
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (drug therapy, metabolism)
• Signal Transduction (drug effects)