Monday, March 23, 2015

Circadian gene expression and extremely low-frequency magnetic fields: An in vitro study

Circadian gene expression and extremely low-frequency magnetic fields: An in vitro study

Manzella, N., Bracci, M., Ciarapica, V., Staffolani, S., Strafella, E., Rapisarda, V., Valentino, M., Amati, M., Copertaro, A. and Santarelli, L. (2015), Circadian gene expression and extremely low-frequency magnetic fields: An in vitro study. Bioelectromagnetics. doi: 10.1002/bem.21915

It is well known that circadian clocks are mainly regulated by light targeting signaling pathways in the hypothalamic suprachiasmatic nucleus. However, an entrainment mediated by non-photic sensory stimuli was also suggested for peripheral clocks. Exposure to extremely low frequency (ELF) electromagnetic fields might affect circadian rhythmicity.

The goal of this research was to investigate effects of ELF magnetic fields (ELF-MF) on circadian clock genes in a human fibroblast cell line.

We found that an ELF-MF (0.1 mT, 50 Hz) exposure was capable of entraining expression of clock genes BMAL1, PER2, PER3, CRY1, and CRY2. Moreover, ELF-MF treatment induced an alteration in circadian clock gene expression previously entrained by serum shock stimulation.  [Note: 0.1 mT = 1,000 milligauss]

These results support the hypothesis that ELF-MF may be able to drive circadian physiologic processes by modulating peripheral clock gene expression.

Diffusion of extremely low frequency electromagnetic fields (ELF-EMF) in the human environment has raised the question of biological effects of EMF on mammalian cells. A large number of studies have reported an effect mediated by ELF-EMF exposure in mT range on processes such as cell proliferation, cell cycle regulation, cell differentiation, metabolism, and various physiological characteristics of cells [Simkó et al., 1998; De Mattei et al., 1999; Mattsson et al., 2001; Harris et al., 2002; Fatigoni et al., 2005; Wolf et al., 2005; Zwirska-Korczala et al., 2005; Polaniak et al., 2010]. However, a certain number of studies have investigated whether ELF-EMF exposure at lower magnetic flux density could result in cell physiology change [Czyz et al., 2004; Shi et al., 2005; Frahm et al., 2006; Mannerling et al., 2010; Markkanen et al., 2010; Luukkonen et al., 2011; Coček et al., 2012; Luukkonen et al., 2014]

It is possible that certain cellular processes, altered by exposure to ELF-EMF, indirectly affect cell physiology [Bułdak et al., 2012; Artacho-Cordón et al., 2013]. Vanderstraeten et al. [2012] hypothesized that ELF-MF contribution to alteration of cell physiological processes might stem from an alteration of circadian rhythmicity.

Circadian rhythms are oscillations characterized by a period length of around 24 h [Reppert and Weaver, 2002]. These endogenously generated rhythms persist in absence of external stimuli and are sustained by a molecular oscillator present in many cells and tissues throughout the organism. Intracellular clocks are regulated by a set of clock genes involved in an autoregulatory transcriptional–translational feedback loop [Reppert and Weaver, 2002; Lowrey and Takahashi, 2004]. In mammalians, the master clock and peripheral clocks work cooperatively [Silver et al., 1996; Hirota and Fukada, 2004]. The central clock is entrained mainly by light-dark cycles, while peripheral clocks can be regulated by nervous and humoral signals (such as glucocorticoids), daily feeding cycle and xenobiotic agents (such as lithium or styrene) exposure [Balsalobre et al., 2000; Osland et al., 2011; Buijs et al., 2013; Manzella et al., 2013; Stevens et al., 2014].

The circadian control system increases fitness and allows organisms to adapt to their physical and ecological environment controlling several biological processes such as proliferation, cell cycle control, and DNA damage repair [De Paula et al., 2008; Borgs et al., 2009; Sancar et al., 2010; Gaddameedhi et al., 2011].

Some alterations of cell physiological processes induced by ELF-EMF exposures might be mediated by modifications of biological clock machinery through variations of clock genes expression. In this paper, we investigated the hypothesis that extremely low frequency magnetic field (ELF-MF) could be associated with alterations of circadian rhythmicity [Vanderstraeten et al., 2012]. In particular we investigated whether an ELF-MF exposure at low magnetic flux density (0.1 mT) was capable of affecting circadian gene expression.
Our findings evidenced that 50 Hz ELF-MF at 0.1 mT acted not only as a trigger in modulating expression of clock genes, but also altered oscillation of gene expression previously triggered by another synchronizer.
These results indicate influence of ELF-MF (0.1 mT, 50 Hz) on circadian clock gene expression according to in vitro evidence of the bio-regulatory capabilities of ELF-MF reported in other studies [Czyz et al., 2004; Frahm et al., 2006; Mannerling et al., 2010; Markkanen et al., 2010; Luukkonen et al., 2011; Coček et al., 2012; Luukkonen et al., 2014].
Therefore, it is our speculation that ELF-MF may be able to affect circadian rhythmicity of many physiologic processes through a modulation in circadian clock gene expression. This in vitro study supports the hypothesis that the circadian clock pathway may act as a mediator between living beings and their physical environment.


Joel M. Moskowitz, Ph.D., Director
Center for Family and Community Health
School of Public Health
University of California, Berkeley

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