Nicotinic acid modulates intracellular calcium concentration and disassembles the cytoskeleton.
Nicotinic acid modulates intracellular calcium concentration and disassembles the cytoskeleton.
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烟酸调节细胞内钙浓度并分解细胞骨架
DOI：
10.3892/mmr.2014.2576
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发表时间：
2014-12
影响因子：
3.4
通讯作者：
Shi Y
中科院分区：
文献类型：
--
作者：
Li J;Li Y;Zhang P;Niu H;Shi Y
烟酸（Nicotinic acid，NA）是维生素B家族的一员，通过降低血浆中低密度脂蛋白胆固醇水平而具有治疗和预防动脉粥样硬化的作用。近年来，NA的主要副作用皮肤潮红也引起了广泛关注。然而，NA在生理学或细胞生物学的其他方面的影响仍然难以捉摸。本研究提供的证据表明，高浓度的NA能够在NIH 3 T3细胞系中首先降低然后升高细胞内[Ca 2 +]。细胞内Ca 2+浓度的降低在最初的10秒内实现，并且在此之前细胞内[Ca 2 +]逐渐升高。值得注意的是，在用70 mM NA处理的NIH 3 T3细胞中观察到核周区域中不透明物质的显著积累。进一步的分析表明，用70 mM NA处理1 h，微管和F-actin细胞骨架系统解体，并导致β-微管蛋白以泛素-蛋白酶体依赖的方式降解。这些数据表明，高浓度的NA破坏细胞骨架结构，这可能有助于负端（核区域），正端（细胞膜区域）定向运输过程，并导致在核周区域的材料沉积。在培养液中加入CaCl_2，随着[Ca ~（2+）]浓度的增加，F-actin的分解受到影响，而对微管的分解没有明显的影响。这些结果表明，细胞骨架系统的破坏不完全是由于NA诱导的[Ca ~（2+）]升高。最后，显微注射NA到非洲爪蟾胚胎中阻断了黑素体向外周细胞区的运输。总之，本研究表明，NA分解F-肌动蛋白和微管系统，从而阻断依赖细胞因子的细胞内运输。
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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影响因子：
2.9
作者：
MORROW, JD;PARSONS, WG;ROBERTS, LJ
通讯作者：
ROBERTS, LJ
影响因子：
15.9
作者：
Benyó, Z;Gille, A;Offermanns, S
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Offermanns, S
影响因子：
82.9
作者：
Tunaru, S;Kero, J;Offermanns, S
通讯作者：
Offermanns, S
影响因子：
4.8
作者：
Aarhus, R;Graeff, RM;Lee, HC
通讯作者：
Lee, HC
影响因子：
4.1
作者：
Wilson, HL;Galione, A
通讯作者：
Galione, A