Blocking of acidosis-mediated apoptosis by a reduction of lactate dehydrogenase activity through antisense mRNA expression

Dae won Jeong, Tae Soo Kim, Joon Won Lee, Ki Tae Kim, Hong Jin Kim, Ik Hwan Kim, Ick Young Kim

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Lactic acid produced from the cells is a potential cause of extra- and intracellular acidification. Due to scarce technical tools, lactic acid that leads to acidification could not be reduced and direct evidence of the relationship between metabolic lactate and apoptosis has not yet been elucidated. In this study, we designed a cellular pH regulation system in CHO cells by a reduction of lactate dehydrogenase (LDH) activity through LDH antisense mRNA expression. This inhibited lactate production and, therefore, acidification of the cytosol. Under HCO3- -buffered growth conditions, both the parent CHO cells and the engineered CHO ceils maintained their extracellular pH and intracellular pH fairly well. However, upon acidification of the cytosol, only the parent CHO cells underwent apoptosis under HCO3-free conditions. In fact, we observed a number of apoptosis-related events only in control cells, including mitochondrial dysfunction, cytochrome c release, and an increase in caspase-3 enzymatic activity.

Original languageEnglish
Pages (from-to)1141-1149
Number of pages9
JournalBiochemical and biophysical research communications
Volume289
Issue number5
DOIs
Publication statusPublished - 2001 Dec 21

Keywords

  • Acidification
  • Anti-sense
  • Apoptosis
  • Lactate dehydrogenase
  • Metabolite

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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