Induction of hepatoma cell apoptosis by c-myc requires zinc and occurs in the absence of DNA fragmentation

Jun Xu, Yang Xu, Quynh Nguyen, Phyllis M. Novikoff, Mark J. Czaja

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Since c-myc expression is increased during apoptosis in toxin-induced liver injury in vivo, the role of c-myc in liver cell apoptosis was investigated. The human hepatoma cell line HuH-7, which constitutively expresses c-myc, was stably transfected with sense and antisense c-myc expression vectors under the control of the zinc-inducible metallothionein promoter. None of the three cell types wild-type, sense c-myc, or antisense c-myc) underwent apoptosis when cultured in serum-free medium (SFM). With the addition of SFM plus 37.5 μM zinc, wild-type and sense c-myc-expressing cells underwent rapid cell death, whereas antisense c-myc-expressing cells exhibited increased survival. This cell death had the light, fluorescent, and electron microscopic appearance of apoptosis, but did not result in DNA fragmentation. This apoptosis could be terminated by the addition of medium containing 2% fetal calf serum or the overexpression of bcl-2 but not by supplementation with specific growth factors. Altering c-myc expression did not affect cellular metallothionein mRNA levels or the rate of cell death from copper or cadmium. The requirement for zinc and absence of DNA fragmentation in c-myc-induced hepatoma cell apoptosis under serum-free conditions provides further evidence of the complex regulation of apoptosis in different cell types.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume270
Issue number1 33-1
StatePublished - 1996

Fingerprint

DNA Fragmentation
Zinc
Hepatocellular Carcinoma
Apoptosis
Cell Death
Serum-Free Culture Media
Metallothionein
Liver
Serum
Cadmium
Copper
Intercellular Signaling Peptides and Proteins
Electrons
Light
Cell Line
Messenger RNA
Survival
Wounds and Injuries

Keywords

  • apoptosis
  • liver

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology

Cite this

Induction of hepatoma cell apoptosis by c-myc requires zinc and occurs in the absence of DNA fragmentation. / Xu, Jun; Xu, Yang; Nguyen, Quynh; Novikoff, Phyllis M.; Czaja, Mark J.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 270, No. 1 33-1, 1996.

Research output: Contribution to journalArticle

@article{d65f072bdc834ef1b3e75c67e6991733,
title = "Induction of hepatoma cell apoptosis by c-myc requires zinc and occurs in the absence of DNA fragmentation",
abstract = "Since c-myc expression is increased during apoptosis in toxin-induced liver injury in vivo, the role of c-myc in liver cell apoptosis was investigated. The human hepatoma cell line HuH-7, which constitutively expresses c-myc, was stably transfected with sense and antisense c-myc expression vectors under the control of the zinc-inducible metallothionein promoter. None of the three cell types wild-type, sense c-myc, or antisense c-myc) underwent apoptosis when cultured in serum-free medium (SFM). With the addition of SFM plus 37.5 μM zinc, wild-type and sense c-myc-expressing cells underwent rapid cell death, whereas antisense c-myc-expressing cells exhibited increased survival. This cell death had the light, fluorescent, and electron microscopic appearance of apoptosis, but did not result in DNA fragmentation. This apoptosis could be terminated by the addition of medium containing 2{\%} fetal calf serum or the overexpression of bcl-2 but not by supplementation with specific growth factors. Altering c-myc expression did not affect cellular metallothionein mRNA levels or the rate of cell death from copper or cadmium. The requirement for zinc and absence of DNA fragmentation in c-myc-induced hepatoma cell apoptosis under serum-free conditions provides further evidence of the complex regulation of apoptosis in different cell types.",
keywords = "apoptosis, liver",
author = "Jun Xu and Yang Xu and Quynh Nguyen and Novikoff, {Phyllis M.} and Czaja, {Mark J.}",
year = "1996",
language = "English (US)",
volume = "270",
journal = "American Journal of Physiology - Renal Fluid and Electrolyte Physiology",
issn = "1931-857X",
publisher = "American Physiological Society",
number = "1 33-1",

}

TY - JOUR

T1 - Induction of hepatoma cell apoptosis by c-myc requires zinc and occurs in the absence of DNA fragmentation

AU - Xu, Jun

AU - Xu, Yang

AU - Nguyen, Quynh

AU - Novikoff, Phyllis M.

AU - Czaja, Mark J.

PY - 1996

Y1 - 1996

N2 - Since c-myc expression is increased during apoptosis in toxin-induced liver injury in vivo, the role of c-myc in liver cell apoptosis was investigated. The human hepatoma cell line HuH-7, which constitutively expresses c-myc, was stably transfected with sense and antisense c-myc expression vectors under the control of the zinc-inducible metallothionein promoter. None of the three cell types wild-type, sense c-myc, or antisense c-myc) underwent apoptosis when cultured in serum-free medium (SFM). With the addition of SFM plus 37.5 μM zinc, wild-type and sense c-myc-expressing cells underwent rapid cell death, whereas antisense c-myc-expressing cells exhibited increased survival. This cell death had the light, fluorescent, and electron microscopic appearance of apoptosis, but did not result in DNA fragmentation. This apoptosis could be terminated by the addition of medium containing 2% fetal calf serum or the overexpression of bcl-2 but not by supplementation with specific growth factors. Altering c-myc expression did not affect cellular metallothionein mRNA levels or the rate of cell death from copper or cadmium. The requirement for zinc and absence of DNA fragmentation in c-myc-induced hepatoma cell apoptosis under serum-free conditions provides further evidence of the complex regulation of apoptosis in different cell types.

AB - Since c-myc expression is increased during apoptosis in toxin-induced liver injury in vivo, the role of c-myc in liver cell apoptosis was investigated. The human hepatoma cell line HuH-7, which constitutively expresses c-myc, was stably transfected with sense and antisense c-myc expression vectors under the control of the zinc-inducible metallothionein promoter. None of the three cell types wild-type, sense c-myc, or antisense c-myc) underwent apoptosis when cultured in serum-free medium (SFM). With the addition of SFM plus 37.5 μM zinc, wild-type and sense c-myc-expressing cells underwent rapid cell death, whereas antisense c-myc-expressing cells exhibited increased survival. This cell death had the light, fluorescent, and electron microscopic appearance of apoptosis, but did not result in DNA fragmentation. This apoptosis could be terminated by the addition of medium containing 2% fetal calf serum or the overexpression of bcl-2 but not by supplementation with specific growth factors. Altering c-myc expression did not affect cellular metallothionein mRNA levels or the rate of cell death from copper or cadmium. The requirement for zinc and absence of DNA fragmentation in c-myc-induced hepatoma cell apoptosis under serum-free conditions provides further evidence of the complex regulation of apoptosis in different cell types.

KW - apoptosis

KW - liver

UR - http://www.scopus.com/inward/record.url?scp=0030051257&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030051257&partnerID=8YFLogxK

M3 - Article

VL - 270

JO - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

JF - American Journal of Physiology - Renal Fluid and Electrolyte Physiology

SN - 1931-857X

IS - 1 33-1

ER -