Pentachlorobutadienyl-L-cysteine uncouples oxidative phosphorylation by dissipating the proton gradient

Journal Article · Fri Sep 15 04:00:00 EDT 1989 · Toxicology and Applied Pharmacology; (USA)

DOI:https://doi.org/10.1016/0041-008X(89)90297-4· OSTI ID:5465789

Schnellmann, R G; Cross, T J; Lock, E A ^[1]

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1. Univ. of Georgia, Athens (USA)

A very early event in the toxicity of pentachlorobutadienyl-L-cysteine (PCBC) to rabbit renal proximal tubules is uncoupling of oxidative phosphorylation. The mechanism of PCBC uncoupling of mitochondrial oxidative phosphorylation has been investigated using isolated rabbit renal cortical mitochondria (RCM). PCBC increased state 4 respiration of RCM respiring on pyruvate/malate or succinate in a concentration (10-100 microM)- and time (1-5 min)-dependent manner. PCBC also increased state 4 respiration in the presence of oligomycin, an inhibitor of F0F1-ATPase. The effect of PCBC on mitochondrial proton permeability was determined by measuring passive mitochondrial swelling. After a 2-min exposure to PCBC, RCM swelled when placed in NH4Cl or NaCl, but not KCl or sucrose. The protonophore carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (FCCP) (1 microM) produced similar effects. After 5 min, RCM swelled when placed in NH4Cl, NaCl, or KCl, but not in sucrose. Aminooxyacetic acid, an inhibitor of cysteine conjugate beta-lyase, blocked the effects of PCBC on respiration, indicating that PCBC can be metabolized by RCM to produce RCM toxicity. These results show that PCBC initially uncouples oxidative phosphorylation by dissipating the proton gradient. Subsequently, additional ion permeabilities occur. These results are in complete agreement with previous observations in rabbit renal proximal tubule suspensions.

• OSTI ID: 5465789
• Journal Information: Toxicology and Applied Pharmacology; (USA), Journal Name: Toxicology and Applied Pharmacology; (USA) Vol. 100:3; ISSN TXAPA; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMALS
BARYONS
BODY
BUTADIENE
CARBOXYLIC ACIDS
CELL CONSTITUENTS
CHEMICAL REACTIONS
CYSTEINE
DIENES
ELEMENTARY PARTICLES
ENZYME INHIBITORS
FERMIONS
HADRONS
HYDROCARBONS
IN VITRO
KIDNEYS
MAMMALS
MITOCHONDRIA
NUCLEONS
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANOIDS
ORGANS
PHOSPHORYLATION
POLYENES
PROTONS
RABBITS
RESPIRATION
TEMPERATURE DEPENDENCE
THIOLS
TIME DEPENDENCE
TOXICITY
TUBULES
VERTEBRATES