Nicotinic acid modulates intracellular calcium concentration and disassembles the cytoskeleton

Li,Jiejing; Li,Yanxi; Zhang,Penghui; Niu,Hua; Shi,Yu

doi:10.3892/mmr.2014.2576

Nicotinic acid modulates intracellular calcium concentration and disassembles the cytoskeleton

Authors:
- Jiejing Li
- Yanxi Li
- Penghui Zhang
- Hua Niu
- Yu Shi
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Affiliations: Department of Clinical Laboratory, Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China, Laboratory of Developmental Diseases in Childhood of Education Ministry, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorder, Children's Hospital of Chongqing Medical University, Chongqing 400014, P.R. China, Clinical Laboratory Centre, The First People's Hospital of Yunnan Province, Kunming, Yunnan 650032, P.R. China
Published online on: September 18, 2014 https://doi.org/10.3892/mmr.2014.2576
Pages: 2805-2810
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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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