The Role of Calcium Affecting Signal Pathway Related to Nitric Oxide-induced Cytotoxicity in H9c2 Cardiac Myoblast.
- Author:
Byung Ho LEE
1
;
Kyung Min JUNG
;
Byoung Kwan AHN
;
Yeun Ja MUN
;
Jay Min OH
;
Jeong Joong KIM
;
Min Kyu CHOI
;
Seung Taeck PARK
;
Yeun Tai CHUNG
Author Information
1. Department of Orthopedic Surgery, School of Medicine, Chosun University, Korea.
- Publication Type:Original Article
- Keywords:
Nitric oxide (NO);
Calcium;
NO-induced cytotoxicity;
Cardiac myoblasts;
NF-kB
- MeSH:
Calcium Channels, L-Type;
Calcium Channels, T-Type;
Calcium*;
Cell Death;
Cytosol;
Diltiazem;
Down-Regulation;
Endoplasmic Reticulum;
Humans;
Myoblasts, Cardiac*;
NF-kappa B;
Nifedipine;
Nitric Oxide;
Nitroprusside;
S-Nitroso-N-Acetylpenicillamine;
Signal Transduction*;
Thapsigargin;
Tissue Donors
- From:Korean Journal of Anatomy
2000;33(5):587-594
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
Nitric oxide (NO) elevates intracellular calcium. But the actions of calcium in NO-induced cell death are not well understood. This study was carried out to investigate the signal transduction pathways of calcium and NO-induced cytotoxicity in H9c2 cardiac myoblasts by using NO donor compounds such as sodium nitroprusside (SNP) and S-nitroso-N-acetylpenicillamine (SNAP). Pretreatment of intracellular calcium chelating agent (BAPTA/AM) or L-type calcium channel blockers (nicardipine, nifedipine, diltiazem and veraparmil) or T-type calcium channel blocker (flunarizine) blocked SNP-induced cytotoxicity respectively only in a three hours. However, thapsigargin (TG), which inhibits endoplasmic reticulum dependent Ca(2+)-ATPase and thereby increases cytosolic Ca(2+), augmented SNP-induced cytotoxicity. The protective effect of BAPTA/AM was inhibited by treatment of protein synthesis inhibitor, cyclohexamide. In addition, pyrrolidine dithiocarbamate (PDTC), NF-kB inhibitor, attenuates the protective effect of BAPTA/AM against SNP-induced cytotoxicity. It is indicated that the protective effect of BAPTA/AM against NO-induced cytotoxicity might be due to the expression of protein related to activation of NFkB. From these results, it is concluded that SNP-induced cytotoxicity is mediated by calcium in a 3 hours via down regulation of protein expression rleated to activation of NFkB.
