ZAKβ Alleviates Oxidized Low-density Lipoprotein (ox-LDL)-Induced Apoptosis and B-type Natriuretic Peptide (BNP) Upregulation in Cardiomyoblast.

Abstract

Oxidized low-density lipoprotein (ox-LDL) is a type of modified cholesterol that promotes apoptosis and inflammation and advances the progression of heart failure. Leucine-zipper and sterile-α motif kinase (ZAK) is a kinase of the MAP3K family which is highly expressed in the heart and encodes two variants, ZAKα and ZAKβ. Our previous study serendipitously found opposite effects of ZAKα and ZAKβ in which ZAKβ antagonizes ZAKα-induced apoptosis and hypertrophy of the heart. This study aims to test the hypothesis of whether ZAKα and ZAKβ are involved in the damaging effects of ox-LDL in the cardiomyoblast. Cardiomyoblast cells H9c2 were treated with different concentrations of ox-LDL. Cell viability and apoptosis were measured by MTT and TUNEL assay, respectively. Western blot was used to detect apoptosis, hypertrophy, and pro-survival signaling proteins. Plasmid transfection, pharmacological inhibition with D2825, and siRNA transfection were utilized to upregulate or downregulate ZAKβ, respectively. Ox-LDL concentration-dependently reduces the viability and expression of several pro-survival proteins, such as phospho-PI3K, phospho-Akt, and Bcl-xL. Furthermore, ox-LDL increases cleaved caspase-3, cleaved caspase-9 as indicators of apoptosis and increases B-type natriuretic peptide (BNP) as an indicator of hypertrophy. Overexpression of ZAKβ by plasmid transfection attenuates apoptosis and prevents upregulation of BNP. Importantly, these effects were abolished by inhibiting ZAKβ either by D2825 or siZAKβ application. Our results suggest that ZAKβ upregulation in response to ox-LDL treatment confers protective effects on cardiomyoblast.

• Authors: Yueh-Min Lin, Jiro Hasegawa Situmorang, Jia-Zun Guan, Dennis Jine-Yuan Hsieh, Jaw-Ji Yang, Michael Yu-Chih Chen, Ching-Hui Loh, Chia-Hua Kuo, Shang-Yeh Lu, Ying-Ming Liou, Chih-Yang Huang
• Journal: Cell biochemistry and biophysics (Cell Biochem Biophys) Vol. 80 Issue 3 Pg. 547-554 (Sep 2022) ISSN: 1559-0283 [Electronic] United States
• PMID: 35776316 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Lipoproteins, LDL
• oxidized low density lipoprotein
• Natriuretic Peptide, Brain
• Protein Kinases
• Map3k20 protein, rat

Topics

• Animals
• Apoptosis
• Hypertrophy
• Lipoproteins, LDL (metabolism, pharmacology)
• Natriuretic Peptide, Brain (genetics)
• Protein Kinases
• Rats
• Up-Regulation