Gap junction blockage promotes cadmium-induced apoptosis in BRL 3A derived from Buffalo rat liver cells

Area of Science:

• Cell Biology
• Toxicology
• Molecular Biology

Background:

• Gap junctions are crucial for cell-to-cell communication.
• Nonessential metals, like cadmium (Cd), can disrupt cellular signaling pathways.
• The precise role of gap junctions in cadmium-induced apoptosis in rat liver cells (BRL 3A) remains unclear.

Purpose of the Study:

• To investigate the role of gap junctions in cadmium-induced apoptosis in BRL 3A rat liver cells.
• To elucidate the molecular mechanisms underlying cadmium's effects on gap junction communication and apoptosis.

Main Methods:

• Cd treatment and its effect on cell index (electrical impedance).
• Assessment of connexin 43 (Cx43) and p-Cx43 expression.
• Measurement of intracellular free Ca(2+) concentration.
• Evaluation of gap junctional intercellular communication.
• Analysis of apoptosis-related proteins (Bax, Bcl-2, caspase-3) and mitochondrial transmembrane electrical potential (Δψm).
• Investigation of mitogen-activated protein kinase (MAPK) pathways (ERK, p38, JNK) activation.

Main Results:

• Cd treatment decreased cell index and gap junctional intercellular communication in BRL 3A cells.
• Cd exposure reduced Cx43 expression while increasing p-Cx43 and intracellular Ca(2+).
• Pretreatment with 18β-glycyrrhizic acid (GA) to block gap junctions enhanced Cd-induced apoptosis, altering Bax, Bcl-2, caspase-3 levels, and Δψm.
• GA treatment amplified ERK and p38 activation during Cd exposure but did not affect JNK activation.

Conclusions:

• Cadmium impairs gap junction communication in BRL 3A cells, contributing to apoptosis.
• Gap junction blockage potentiates cadmium-induced apoptosis through modulation of apoptosis-related proteins and mitochondrial pathways.
• The ERK and p38 signaling pathways are implicated in the enhanced apoptosis observed when gap junctions are blocked during cadmium exposure.