Nicotinic acid modulates intracellular calcium concentration and disassembles the cytoskeleton

Area of Science:

• Cell Biology
• Biochemistry
• Molecular Biology

Background:

• Nicotinic acid (NA), a Vitamin B derivative, is known for its role in managing atherosclerosis by lowering LDL cholesterol.
• The major side effect of NA, cutaneous flushing, has garnered attention, but its broader cellular effects remain largely unexplored.

Purpose of the Study:

• To investigate the effects of high nicotinic acid concentrations on intracellular calcium levels and cytoskeleton dynamics in NIH3T3 cells.
• To elucidate the mechanisms by which NA affects cellular transport and structure.

Main Methods:

• Treatment of NIH3T3 cells with high concentrations of NA (70 mM).
• Measurement of intracellular calcium ([Ca2+]) levels.
• Analysis of microtubule and F-actin cytoskeleton integrity using microscopy.
• Investigation of β-tubulin degradation via the ubiquitin-proteasome pathway.
• Microinjection of NA into Xenopus embryos to assess melanosome transport.

Main Results:

• High NA concentrations initially reduced then elevated intracellular [Ca2+].
• 70 mM NA treatment disassembled microtubule and F-actin cytoskeleton, leading to β-tubulin degradation.
• NA-induced cytoskeleton disruption impaired cytoskeleton-dependent intracellular transport, evidenced by perinuclear material accumulation and blocked melanosome transport.
• Elevated intracellular [Ca2+] partially contributed to F-actin disassembly but not microtubule disruption.

Conclusions:

• Nicotinic acid at high concentrations disrupts both microtubule and F-actin cytoskeleton systems.
• NA-induced cytoskeleton disassembly leads to the blockage of essential cytoskeleton-dependent intracellular transport processes.
• These findings reveal novel cellular mechanisms of NA action beyond its lipid-lowering effects.