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Nicotinic acid modulates intracellular calcium concentration and disassembles the cytoskeleton.

Li J, Li Y, Zhang P, Niu H, Shi Y - Mol Med Rep (2014)

Bottom Line: Artificially increasing [Ca2+] adding CaCl2 to the culture media effected the disassembly of F‑actin, while it had no apparent effect on microtubules.These results suggested that the disruption of the cytoskeleton systems was not entirely due to the NA-induced elevation of [Ca2+].In conclusion, the present study indicated that NA disassembles F‑actin and microtubule systems, thereby blocking cytoskeleton-dependent intracellular transport.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China.

ABSTRACT
Nicotinic acid (NA), a member of the vitamin B family, is well known for its functions in the treatment and prevention of atherosclerosis due to decreasing plasma levels of low-density lipoprotein cholesterol. In recent years, the major side effect of NA, cutaneous flushing, has also attracted extensive attention. However, the effects of NA in other aspects of physiology or cell biology have remained elusive. The present study provided evidence that high concentrations of NA were able to first reduce and later elevate intracellular [Ca2+] in the NIH3T3 cell line. The reduction of the intracellular Ca2+ concentration was achieved within the initial 10 sec, and was preceded by a gradual elevation of intracellular [Ca2+]. Notably, marked accumulation of opaque materials in the perinuclear region was observed in NIH3T3 cells treated with 70 mM NA. Further analysis revealed that treatment with 70 mM NA for 1 h disassembled the microtubule and F‑actin cytoskeleton systems and resulted in β‑tubulin degradation in an ubiquitin‑proteasome-dependent manner. These data indicated that high concentrations of NA disrupted cytoskeleton structures, which may have contributed to minus end (nucleus region) to plus end (cell membrane region)-directed transport processes and resulted in the deposition of material in the perinuclear region. Artificially increasing [Ca2+] adding CaCl2 to the culture media effected the disassembly of F‑actin, while it had no apparent effect on microtubules. These results suggested that the disruption of the cytoskeleton systems was not entirely due to the NA-induced elevation of [Ca2+]. Finally, microinjection of NA into xenopus embryos blocked the transport of melanosomes to the peripheral cellular area. In conclusion, the present study indicated that NA disassembles F‑actin and microtubule systems, thereby blocking cytoskeleton-dependent intracellular transport.

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Related in: MedlinePlus

External addition of CaCl2 to the culture media and 1 h incubation disrupted the F-actin filaments, stained with Texas Red-X phalloidin, but did not affect the microtubules, stained with fluorescein isothiocyanate-conjugated antibody. (Magnification, ×250).
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f3-mmr-10-06-2805: External addition of CaCl2 to the culture media and 1 h incubation disrupted the F-actin filaments, stained with Texas Red-X phalloidin, but did not affect the microtubules, stained with fluorescein isothiocyanate-conjugated antibody. (Magnification, ×250).

Mentions: To further elucidate the association between changes in [Ca2+] and the disassembly of the cytoskeleton, a CaCl2 solution was added directly into the NIH3T3 cell culture media and the cytoskeleton structure was examined following 1 h of incubation. Consistent with the effect of NA demonstrated above, 40 mM CaCl2 disrupted F-actin filaments (Fig. 3A) into punctuate G-actin spots (Fig. 3D). However, artificial increases in [Ca2+] did not affect the microtubular structure (Fig. 3E) compared with that of the control group (Fig. 3B). The results implied that the Ca2+ wave induced by NA may be involved in the disruption of F-actin filaments, but not in the disassembly of the microtubular polymer structure.


Nicotinic acid modulates intracellular calcium concentration and disassembles the cytoskeleton.

Li J, Li Y, Zhang P, Niu H, Shi Y - Mol Med Rep (2014)

External addition of CaCl2 to the culture media and 1 h incubation disrupted the F-actin filaments, stained with Texas Red-X phalloidin, but did not affect the microtubules, stained with fluorescein isothiocyanate-conjugated antibody. (Magnification, ×250).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4227433&req=5

f3-mmr-10-06-2805: External addition of CaCl2 to the culture media and 1 h incubation disrupted the F-actin filaments, stained with Texas Red-X phalloidin, but did not affect the microtubules, stained with fluorescein isothiocyanate-conjugated antibody. (Magnification, ×250).
Mentions: To further elucidate the association between changes in [Ca2+] and the disassembly of the cytoskeleton, a CaCl2 solution was added directly into the NIH3T3 cell culture media and the cytoskeleton structure was examined following 1 h of incubation. Consistent with the effect of NA demonstrated above, 40 mM CaCl2 disrupted F-actin filaments (Fig. 3A) into punctuate G-actin spots (Fig. 3D). However, artificial increases in [Ca2+] did not affect the microtubular structure (Fig. 3E) compared with that of the control group (Fig. 3B). The results implied that the Ca2+ wave induced by NA may be involved in the disruption of F-actin filaments, but not in the disassembly of the microtubular polymer structure.

Bottom Line: Artificially increasing [Ca2+] adding CaCl2 to the culture media effected the disassembly of F‑actin, while it had no apparent effect on microtubules.These results suggested that the disruption of the cytoskeleton systems was not entirely due to the NA-induced elevation of [Ca2+].In conclusion, the present study indicated that NA disassembles F‑actin and microtubule systems, thereby blocking cytoskeleton-dependent intracellular transport.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China.

ABSTRACT
Nicotinic acid (NA), a member of the vitamin B family, is well known for its functions in the treatment and prevention of atherosclerosis due to decreasing plasma levels of low-density lipoprotein cholesterol. In recent years, the major side effect of NA, cutaneous flushing, has also attracted extensive attention. However, the effects of NA in other aspects of physiology or cell biology have remained elusive. The present study provided evidence that high concentrations of NA were able to first reduce and later elevate intracellular [Ca2+] in the NIH3T3 cell line. The reduction of the intracellular Ca2+ concentration was achieved within the initial 10 sec, and was preceded by a gradual elevation of intracellular [Ca2+]. Notably, marked accumulation of opaque materials in the perinuclear region was observed in NIH3T3 cells treated with 70 mM NA. Further analysis revealed that treatment with 70 mM NA for 1 h disassembled the microtubule and F‑actin cytoskeleton systems and resulted in β‑tubulin degradation in an ubiquitin‑proteasome-dependent manner. These data indicated that high concentrations of NA disrupted cytoskeleton structures, which may have contributed to minus end (nucleus region) to plus end (cell membrane region)-directed transport processes and resulted in the deposition of material in the perinuclear region. Artificially increasing [Ca2+] adding CaCl2 to the culture media effected the disassembly of F‑actin, while it had no apparent effect on microtubules. These results suggested that the disruption of the cytoskeleton systems was not entirely due to the NA-induced elevation of [Ca2+]. Finally, microinjection of NA into xenopus embryos blocked the transport of melanosomes to the peripheral cellular area. In conclusion, the present study indicated that NA disassembles F‑actin and microtubule systems, thereby blocking cytoskeleton-dependent intracellular transport.

Show MeSH
Related in: MedlinePlus