Melatonin protects against cadmium-induced oxidative stress via mitochondrial STAT3 signaling in human prostate...

Area of Science:

• Biochemistry
• Environmental Toxicology
• Cell Biology

Background:

• Cadmium (Cd) is an environmental toxicant causing cellular damage via reactive oxygen species (ROS) and mitochondrial dysfunction.
• The protective mechanisms of melatonin against Cd toxicity are not fully understood.

Purpose of the Study:

• To elucidate the mechanism by which melatonin protects against Cadmium-induced toxicity.
• To investigate the role of mitochondrially-localized signal transducer and activator of transcription 3 (mitoSTAT3) in Cadmium toxicity and melatonin's protective effects.

Main Methods:

• Utilized human prostate stromal cells and mouse embryonic fibroblasts to study Cadmium exposure and melatonin treatment.
• Assessed levels of mitoSTAT3 and GRIM-19 (an electron transport chain component) in response to Cadmium and melatonin.
• Evaluated reactive oxygen species (ROS) production, mitochondrial function, and cell viability.
• Conducted in vivo studies using mouse prostate tissue.

Main Results:

• Cadmium exposure reduced levels of mitoSTAT3 and GRIM-19 in cells.
• Melatonin treatment increased mitoSTAT3 abundance in Cadmium-exposed cells, mitigating ROS damage, mitochondrial dysfunction, and cell death.
• Melatonin also increased mitochondrial GRIM-19 levels, which were downregulated by Cadmium.
• In vivo, melatonin reversed Cadmium-induced reductions in prostate tissue size and levels of mitoSTAT3 and GRIM-19.

Conclusions:

• Melatonin protects against Cadmium-induced cytotoxicity by regulating mitoSTAT3 function within mitochondria.
• Melatonin preserves mitochondrial function and reduces oxidative stress during Cadmium exposure.
• The findings highlight a novel mechanism involving mitoSTAT3 and GRIM-19 in Cadmium toxicity and melatonin's protective role.