Naproxen-induced Ca2+ movement and death in MDCK canine renal tubular cells

Area of Science:

• Pharmacology
• Cell Biology
• Toxicology

Background:

• Naproxen, an anti-inflammatory drug, is known to affect cellular calcium ion (Ca(2+)) homeostasis.
• Understanding naproxen's impact on renal tubular cells is crucial for assessing its safety and mechanisms of action.

Purpose of the Study:

• To investigate the effects of naproxen on intracellular calcium ([Ca(2+)](i)) levels and cell viability in Madin-Darby canine kidney (MDCK) cells.
• To elucidate the specific mechanisms by which naproxen influences Ca(2+) signaling and induces cell death.

Main Methods:

• Exposure of MDCK cells to varying concentrations of naproxen.
• Measurement of intracellular Ca(2+) ([Ca(2+)](i)) using fluorescent indicators.
• Assessment of cell viability and apoptosis using Annexin V/propidium iodide staining.
• Utilizing various pharmacological inhibitors and modulators of Ca(2+) channels and signaling pathways.

Main Results:

• Naproxen induced a concentration-dependent rise in [Ca(2+)](i) in MDCK cells.
• The Ca(2+) signal involved Ca(2+) release from intracellular stores (including endoplasmic reticulum) and influx via nifedipine-sensitive channels.
• Naproxen caused concentration-dependent cell death, characterized by apoptosis, at lower concentrations than those affecting Ca(2+) homeostasis.

Conclusions:

• Naproxen disrupts Ca(2+) homeostasis in MDCK cells through a combination of intracellular Ca(2+) release and nifedipine-sensitive Ca(2+) channel-mediated influx.
• Naproxen induces apoptosis and cell death in MDCK renal tubular cells.
• These findings highlight potential cellular mechanisms underlying naproxen's effects on kidney cells.