Lead induces mouse skin fibroblast apoptosis by disrupting intracellular homeostasis

Area of Science:

• Toxicology
• Cell Biology
• Dermatology

Background:

• Lead (Pb) is a pervasive industrial and environmental contaminant.
• Pb exposure can induce pathophysiological changes across multiple cellular and organ systems.
• Mechanisms of Pb-induced skin cell damage remain incompletely understood.

Purpose of the Study:

• To investigate the apoptotic effects of lead (Pb) on mouse skin fibroblasts (MSF) in vitro.
• To elucidate the cellular mechanisms underlying Pb-induced cytotoxicity in skin cells.

Main Methods:

• MSF were treated with varying concentrations of Pb (40–160 μM) for 24 hours.
• Assessed morphological changes, DNA damage, caspase activity (caspase-3, -8, -9), intracellular calcium (Ca2+), reactive oxygen species (ROS), mitochondrial membrane potential, and cell cycle progression.
• Analyzed gene expression of apoptosis-related proteins (Bax, Bcl-2, Fas, p53).

Main Results:

• Pb treatment induced significant morphological alterations and DNA damage in MSF.
• Apoptosis was observed in a dose- and time-dependent manner, with increased caspase activities and apoptotic cell populations.
• Pb exposure elevated intracellular Ca2+ and ROS levels, decreased mitochondrial membrane potential, and caused G0/G1 cell cycle arrest.
• Upregulation of Bax, Fas, caspase-3, -8, and p53, and downregulation of Bcl-2 gene expression were noted.

Conclusions:

• Lead exposure triggers apoptosis in mouse skin fibroblasts by disrupting intracellular homeostasis.
• Pb-induced cytotoxicity involves the intrinsic and extrinsic apoptotic pathways and mitochondrial dysfunction.
• Findings enhance understanding of Pb's toxicological mechanisms on skin fibroblasts, informing future risk assessments.