Disease relevance of Ccbl1

• Inhibition of cysteine-S-conjugate beta-lyase reduced the toxicity of each of the cisplatin-conjugates [1].
• Previous studies have revealed that GTK, a Src-like protein tyrosine kinase expressed in beta cells (also named Bsk/Iyk), regulates multiple responses including growth and survival of rat insulinoma cells (RINm5F) and differentiation of neuronal PC12 cells [2].

High impact information on Ccbl1

• These findings support the hypothesis that a mitochondrial cysteine S-conjugate beta-lyase converts the cisplatin-cysteine S-conjugate to a toxicant, and the data are consistent with the hypothesis that mitAspAT plays a role in the bioactivation of cisplatin [3].
• The final step in the proposed bioactivation is the formation of a platinum-cysteine S-conjugate followed by a pyridoxal 5'-phosphate (PLP)-dependent cysteine S-conjugate beta-lyase reaction [3].
• Decreased expression of kynurenine aminotransferase-I (KAT-I) in the substantia nigra of mice after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment [4].
• Cysteine S-conjugate beta-lyase was inhibited by aminooxyacetic acid (AOAA) [5].
• Increased cytokine-induced cytotoxicity of pancreatic islet cells from transgenic mice expressing the Src-like tyrosine kinase GTK [2].

Biological context of Ccbl1

• The conversion of methyl isothiocyanate to S-methyl metam and its oxon probably involves conjugation with glutathione, hydrolysis to S-(N-methylthiocarbamoyl)-cysteine, cleavage by cysteine conjugate beta-lyase to release metam, and finally methylation and oxidative desulfuration [6].

Anatomical context of Ccbl1

• CONCLUSIONS: These results suggest that although GTK increases the beta-cell mass, it also enhances islet cell death in response to cytokines and may thus be involved in the beta-cell damage in type 1 diabetes [2].
• 3. Cysteine conjugate beta-lyase was present in mitochondria and cytosol from mouse liver and kidney [7].

Associations of Ccbl1 with chemical compounds

• By contrast, pretreatment of mice with the cysteine conjugate beta-lyase inhibitor, (aminooxy)acetic acid (100 mg/kg, ip), 1 hr before APAP did not alter nephrotoxicity [8].
• A substantial fraction of HCBD cysteine S-conjugate thus concentrated in the kidney is metabolized by renal cysteine conjugate beta-lyase to reactive intermediates [9].
• Both the renal accumulation by the organic anion transporter and the topographical distribution of cysteine conjugate beta-lyase along the nephron are major determinants of organ and cell selectivity [10].

References