Transport of S-cysteine conjugates in LL-PK/sub 1/ cells and its role in toxicity

Conference · Thu May 01 04:00:00 EDT 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6937027

Schaeffer, V; Stevens, J

In order to study its role in S-cysteine conjugate toxicity, the transport of the nephrotoxic cysteine conjugate, S-1,2-dichlorovinyl-L-cysteine (L-DCVC), was investigated in the kidney cell line, LLC-PK1. When incubated with (/sup 35/S)-DCVC, accumulation of radioactivity within the cells was linear for at least 5 min with 92% of the /sup 35/S present as unmetabolized L-DCVC. Kinetic analysis indicated two saturable uptake systems; Km = 6.8 ..mu..M and 1.6 mM; V/sub max/ = .048 and 1.4 nmol/min/mg protein. Both systems were Na/sup +/-independent and were inhibited by amino acid transport system L substrates but not substrates of systems A, ASC or organic anion transport. L-DCVC uptake at 5 ..mu..M and 500 ..mu..M was significantly greater in subconfluent cells than in confluent cultures by 5 and 2.8 fold, respectively. The presence of the non-toxic conjugates S-methyl-(SMC), S-ethyl-(SEC), S-benzyl-L- cysteine (SBC) and the D isomer of DCVC blocked the toxicity and inhibited the transport of L-DCVC in LLC-PK1 cells in the rank order of SBC > SEC congruent to D-DCVC > SMC. The metabolism of L-DCVC, previously shown to be required for cytotoxicity, was only slightly inhibited by these conjugates and did not correlate with their relative protection against toxicity. This study suggests that L-DCVC is transported into these cells by the system L transporter and that protection against toxicity by non-toxic S-cysteine conjugates is due to the inhibition of transport.

• Research Organization: Federal Drug Administration, Bethesda, MD
• OSTI ID: 6937027
• Report Number(s): CONF-8606151-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CARBOXYLIC ACIDS
CYSTEINE
DAYS LIVING RADIOISOTOPES
EVEN-ODD NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KIDNEYS
KINETICS
LIGHT NUCLEI
MEMBRANE TRANSPORT
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
RADIOISOTOPES
REACTION KINETICS
SUBSTRATES
SULFUR 35
SULFUR ISOTOPES
THIOLS
TOXICITY
TRACER TECHNIQUES