Báo cáo khoa học: Long-term extracellular signal-related kinase activation following cadmium intoxication is negatively regulated by a protein kinase C-dependent pathway affecting cadmium transport

Long-term extracellular signal-related kinase activation following cadmium intoxication is negatively regulated by a protein kinase C-dependent pathway affecting cadmium transport

Authors: Patrick Martin, Kim E. Boulukos, Marie C. Poggi and Philippe Pognonec

Affiliation: CNRS FRE3094, Université de Nice Sophia Antipolis, France

Keywords: cadmium; extracellular signal-related kinase (ERK); protein kinase C (PKC); sustained activation; ZIP8

Abstract: This study investigates the mechanisms underlying sustained extracellular signal-related kinase (ERK) activation induced by low-dose cadmium exposure. The research demonstrates that this prolonged ERK activation, which is linked to cell death, is negatively regulated by protein kinase C (PKC). Specifically, activation of PKC, particularly the PKCε isotype, inhibits cadmium-induced sustained ERK activation and confers protection against cadmium toxicity. Conversely, inhibiting PKC enhances ERK activation and cadmium toxicity. The findings suggest that PKC acts through a “hit-and-run” mechanism, independent of protein synthesis, to modify the activity of the ZIP8 cadmium transporter. This modification reduces cadmium influx and consequently dampens the sustained ERK response, thereby protecting cells from cadmium poisoning. The study proposes an integrative model illustrating the distinct pathways of transient and sustained ERK activation and the role of PKC and ZIP8 in regulating the latter.

Table of Contents:

• Keywords
• Correspondence
• Abbreviations
• Abstract
• Introduction
• Results
• Discussion
• Experimental procedures
• References