The effects of haloalkene cysteine conjugates on cytosolic free calcium levels in suspensions of rat renal proximal tubules

Carlotta E. Groves, Edward A. Lock, Rick G. Schnellmann

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Disturbances in intracellular calcium homeostasis may play a role in the injury induced by various haloalkene cysteine conjugates. The effects of S‐(1,2,3,4,4‐pentachloro‐1,3‐butadienyl)‐L‐cysteine (PCBC), S‐(1,2‐dichlorovinyl)‐L‐cysteine (DCVC), and S‐(1,1,2,2‐tetrafluoroethyl)‐L‐cysteine (TFEC) on cytosolic free calcium levels were examined in suspensions of rat renal proximal tubules. Cytosolic free calcium levels, measured with fura 2, in control tubules, were 112 ± 3 nM and increased more than 200% within 1 minute after exposure to the calcium ionophore ionomycin (0.005 mM). PCBC (0.1 mM) increased cytosolic free calcium levels 18% after 5 minutes, while tubular oxygen consumption was unaffected. DCVC (1 mM) did not alter tubular cytosolic free calcium levels or oxygen consumption under similar conditions. TFEC (1 mM) increased cytosolic free calcium levels 36%, had no effect on basal oxygen consumption, and decreased nystatin‐stimulated oxygen consumption 30% after 5 minutes. TFEC increased cytosolic free calcium levels in tubules incubated in a nominally calcium‐free buffer but not in a calcium containing buffer in the presence of EGTA. The data suggest that the TFEC‐induced increase in cytosolic free calcium levels may result from an influx of extracellular calcium or from inhibition of calcium efflux. The increase in cytosolic free calcium levels preceded changes in basal oxygen consumption in tubules exposed to PCBC and TFEC. This study shows that an increase in cytosolic free calcium levels is an early event following PCBC and TFEC but not DCVC exposure.

Original languageEnglish (US)
Pages (from-to)187-192
Number of pages6
JournalJournal of biochemical toxicology
Volume5
Issue number3
DOIs
StatePublished - 1990
Externally publishedYes

Keywords

  • Cytosolic Free Calcium
  • Dichlorovinyl‐L‐cysteine
  • Haloalkene Cysteine Conjugates
  • Pentachlorobutadienyl‐L‐cysteine
  • Rat Renal Proximal Tubules
  • Tetrafluoroethyl‐L‐cysteine

ASJC Scopus subject areas

  • Toxicology

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