Parthenolide regulates oxidative stress-induced mitophagy and suppresses apoptosis through p53 signaling pathway in C2C12 myoblasts.

Abstract

Muscle redox disturbances and oxidative stress have emerged as a common pathogenetic mechanism and potential therapeutic intervention in some muscle diseases. Parthenolide (PTL), a sesquiterpene lactone found in large amounts in the leaves of feverfew, possesses anti-inflammatory, anti-migraine, and anticancer properties. Although PTL was reported to alleviate cancer cachexia and improve skeletal muscle characteristics in a cancer cachexia model, its actions on oxidative stress-induced damage in C2C12 myoblasts have not been reported and the regulatory mechanisms have not yet been defined. In our study, PTL attenuated H2 O2 -induced growth inhibition and morphological changes. Furthermore, PTL exhibited scavenging activity against reactive oxygen species and protected C2C12 cells from apoptosis in response to H2 O2 . Meanwhile, PTL suppressed collapse of the mitochondrial membrane potential, thereby contributing to normalizing H2 O2 -induced autophagy flux and mitophagy, correlating with inhibiting degradation of mitochondrial marker protein TIM23, the increase in LC3-II expression and the reduction of mitochondria DNA. Besides its protective effect on mitochondria, PTL also prevented H2 O2 -induced lysosomes damage in C2C12 cells. In addition, the phosphorylation of p53, cathepsin B, and Bax/Bcl-2 protein levels, and the translocation of Bax from the cytosol to mitochondria induced by H2 O2 in C2C12 cells was significantly reduced by PTL. In conclusion, PTL modulates oxidative stress-induced mitophagy and protects C2C12 myoblasts against apoptosis, suggesting a potential protective effect against oxidative stress-associated skeletal muscle diseases.

• Authors: Yinghui Ren, Yan Li, Jienv Lv, Xiangdong Guo, Jieyou Zhang, Dongmei Zhou, Zimu Zhang, Zhenyi Xue, Guangze Yang, Qing Xi, Hongkun Liu, Zehan Liu, Lijuan Zhang, Qi Zhang, Zhi Yao, Rongxin Zhang, Yurong Da
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 120 Issue 9 Pg. 15695-15708 (09 2019) ISSN: 1097-4644 [Electronic] United States
• PMID: 31144365 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Wiley Periodicals, Inc.

Chemical References

• Mitochondrial Membrane Transport Proteins
• Mitochondrial Precursor Protein Import Complex Proteins
• Reactive Oxygen Species
• Sesquiterpenes
• Timm23 protein, mouse
• Tumor Suppressor Protein p53
• parthenolide
• Hydrogen Peroxide

Topics

• Animals
• Apoptosis (drug effects)
• Humans
• Hydrogen Peroxide (metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mitochondria (drug effects, genetics)
• Mitochondrial Membrane Transport Proteins (genetics)
• Mitochondrial Precursor Protein Import Complex Proteins
• Mitophagy (drug effects, genetics)
• Muscular Diseases (drug therapy, genetics, metabolism, pathology)
• Myoblasts (drug effects)
• Oxidative Stress (drug effects)
• Reactive Oxygen Species (metabolism)
• Sesquiterpenes (pharmacology)
• Signal Transduction (drug effects)
• Tumor Suppressor Protein p53 (genetics)