Korean J Anat.  2000 Oct;33(5):587-594.

The Role of Calcium Affecting Signal Pathway Related to Nitric Oxide-induced Cytotoxicity in H9c2 Cardiac Myoblast

• Lee BH
• Jung KM
• Ahn BK
• Mun YJ
• Oh JM
• Kim JJ
• Choi MK
• Park ST
• Chung YT

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.

Keyword

Nitric oxide (NO); Calcium; NO-induced cytotoxicity; Cardiac myoblasts; NF-kB

MeSH Terms

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
Calcium
Calcium Channels, L-Type
Calcium Channels, T-Type
Diltiazem
NF-kappa B
Nifedipine
Nitric Oxide
Nitroprusside
S-Nitroso-N-Acetylpenicillamine
Thapsigargin