ABSTRACT
Abstract Curcumin (diferuloylmethane), a pharmacologically active substance derived from turmeric, exhibits anti-inflammatory, anticarcinogenic, and antioxidant properties. We examined the modulation of oxidative-stress resistance and associated regulatory mechanisms by curcumin in a Caenorhabditis elegans model. Our results showed that curcumin-treated wild-type C. elegans exhibited increased survival during juglone-induced oxidative stress compared with the control treatment. In addition, curcumin reduced the levels of intracellular reactive oxygen species in C. elegans. Moreover, curcumin induced the expression of the gst-4 and hsp-16.2 stress response genes. Lastly, our findings from the mechanistic study in this investigation suggest that the antioxidative effect of curcumin is mediated via regulation of age-1, akt-1, pdk-1, osr-1, unc-43, sek-1, skn-1, sir-2.1, and mev-1. Our study elucidates the diverse modes of action and signaling pathways that underlie the antioxidant activity exhibited by curcumin in vivo.
Subject(s)
Caenorhabditis elegans Proteins/genetics , Curcumin/pharmacology , Oxidative Stress/drug effects , Animals , Caenorhabditis elegans , Caenorhabditis elegans Proteins/metabolism , Oxidative Stress/genetics , Phosphorylation , Reactive Oxygen Species/metabolism , Signal Transduction/drug effectsABSTRACT
Screening for differentially expressed genes is a straightforward approach to study the molecular basis for changes in gene expression. Differential display analysis has been used by investigators in diverse fields of research since it was developed. Differential display has also been the approach of choice to investigate changes in gene expression in response to various biological challenges in invertebrates. We review the application of differential display analysis of gene expression in invertebrates, and provide a specific example using this technique for novel gene discovery in the nematode Caenorhabditis elegans.
Subject(s)
Gene Expression Profiling , Invertebrates/genetics , Animals , Cadmium/metabolism , Caenorhabditis elegans/genetics , Caenorhabditis elegans/physiology , Gene Expression RegulationABSTRACT
A homologue of pyruvate carboxylase was isolated as an expressed sequence tag during the identification of cadmium-responsive genes in Caenorhabditis elegans. The C. elegans protein, designated PYC-1, is predicted to contain 1,175 amino acids with a molecular mass of 129,284. Amino acid sequence analysis indicates that PYC-1 will be translocated into mitochondria. PYC-1 has high levels of amino acid sequence identity with other pyruvate carboxylases. The highest levels of identity are in the putative transcarboxylation, biotin carboxylation and biotin carboxyl carrier domains.
Subject(s)
Cadmium/pharmacology , Caenorhabditis elegans/genetics , Gene Expression Regulation, Enzymologic/drug effects , Pyruvate Carboxylase/genetics , Amino Acid Sequence , Animals , Base Sequence , Caenorhabditis elegans/enzymology , Isoenzymes , Molecular Sequence Data , Pyruvate Carboxylase/metabolism , Sequence AlignmentABSTRACT
The transition metal cadmium is a pervasive and persistent environmental contaminant that has been shown to be both a human toxicant and carcinogen. To inhibit cadmium-induced damage, cells respond by increasing the expression of genes encoding stress-response proteins. In most cases, the mechanism by which cadmium affects the expression of these genes remains unknown. It has been demonstrated in several instances that cadmium activates gene transcription through signal transduction pathways, mediated by protein kinase C, cAMP-dependent protein kinase, or calmodulin. A codicil is that cadmium should influence the expression of numerous genes. To investigate the ability of cadmium to affect gene transcription, the differential display technique was used to analyze gene expression in the nematode Caenorhabditis elegans. Forty-nine cDNAs whose steady-state levels of expression change 2-6-fold in response to cadmium exposure were identified. The nucleotide sequences of the majority of the differentially expressed cDNAs are identical to those of C. elegans cosmids, yeast artificial chromosomes, expressed sequence tags, or predicted genes. The translated amino acid sequences of several clones are identical to C. elegans metallothionein-1, HSP70, collagens, and rRNAs. In addition, C. elegans homologues of pyruvate carboxylase, DNA gyrase, beta-adrenergic receptor kinase, and human hypothetical protein KIAA0174 were identified. The translated amino acid sequences of the remaining differentially expressed cDNAs encode novel proteins.
