Résumé
BACKGROUND: Heavy metals can cause great harm to Siberian tigers in the natural environment. Cadmium (Cd2+) is an environmental contaminant that affects multiple cellular processes, including cell proliferation, differentiation, and survival. It has been shown to induce apoptosis in a variety of cell types and tissues. RESULTS: We investigated the apoptotic effects of Cd2+ on Siberian tiger fibroblasts in vitro. Our research revealed the typical signs of apoptosis after Cd²+ exposure. Apoptosis was dose- (0-4.8 µM) and duration-dependent (12-48 h), and proliferation was strongly inhibited. Cd²+ increased the activity of caspase-3, -8, and -9 and disrupted calcium homeostasis by causing oxidative stress and mitochondrial dysfunction. It also increased K+ efflux and altered the mRNA levels of Bax, Bcl-2, caspase-3, caspase-8, Fas, and p53. CONCLUSIONS: Our results suggest that Cd2+ triggers the apoptosis of Siberian tiger fibroblasts by disturbing intracellular homeostasis. These results will aid in our understanding of the effects of Cd2+ on Siberian tigers and in developing interventions to treat and prevent cadmium poisoning.
Sujets)
Animaux , Cadmium/toxicité , Apoptose/effets des médicaments et des substances chimiques , Espace intracellulaire/effets des médicaments et des substances chimiques , Tigres , Fibroblastes/effets des médicaments et des substances chimiques , Homéostasie/effets des médicaments et des substances chimiques , Sibérie , Altération de l'ADN , Cycle cellulaire/effets des médicaments et des substances chimiques , Cellules cultivées , Réaction de polymérisation en chaîne , Espèces réactives de l'oxygène/analyse , Apoptose/génétique , Caspases/analyse , Caspases/effets des médicaments et des substances chimiques , Test des comètes/médecine vétérinaire , Microscopie électronique à transmission , Transcription inverse , Potentiel de membrane mitochondriale/effets des médicaments et des substances chimiques , Fibroblastes/physiologie , Homéostasie/physiologieSujets)
Animaux , Rats , Facteur atrial natriurétique/métabolisme , Calcium/pharmacologie , Myocytes cardiaques/effets des médicaments et des substances chimiques , Myocytes cardiaques/enzymologie , Poly(ADP-ribose) polymerases/métabolisme , Angiotensine-II/pharmacologie , Animaux nouveau-nés , Facteur atrial natriurétique/génétique , Calcium/métabolisme , Activation enzymatique/effets des médicaments et des substances chimiques , Extracellular Signal-Regulated MAP Kinases/métabolisme , /métabolisme , Régulation de l'expression des gènes/effets des médicaments et des substances chimiques , Espace intracellulaire/effets des médicaments et des substances chimiques , Espace intracellulaire/métabolisme , Contraction myocardique/effets des médicaments et des substances chimiques , Phosphorylation/effets des médicaments et des substances chimiques , Régions promotrices (génétique)/génétique , Liaison aux protéines/effets des médicaments et des substances chimiques , Protéines proto-oncogènes c-fos/génétique , Protéines proto-oncogènes c-fos/métabolisme , Rat Sprague-Dawley , Ribose/métabolismeRésumé
The heme-regulated inhibitor (HRI), a member of the eIF-2 kinase family is crucial for regulating protein synthesis during stress. In addition to heme, stress proteins Hsp90 and Hsp70 are known to regulate HRI. The present study aims to determine the physical association of these Hsps in the regulation of HRI activation during oxidative stress using human K562 cells as a model. Extracts from the stress-induced cells were used for determining HRI kinase activity by measuring eIF-2 phosphorylation, and Hsp-HRI interaction by immunoprecipitation and immunoblot analyses. The results indicate a significant increase in both Hsp70 and Hsp90 expression during AAPH (2, 2’-azobis (2-amidinopropane) dihydrochloride)-induced oxidative stress. Further, their interaction with HRI, which correlates well with its increased HRI kinase activity leads to inhibition of protein synthesis. Thus, we demonstrate that Hsps play an important role in the regulation of initiation of protein synthesis during oxidative stress.