Abstract
Electrical current at physiological strength has been applied as a therapeutic approach for various diseases. Several of our works showed that mild electrical stimulation (MES) at 0.1-ms pulse width has positive impact on organisms. But despite the growing evidence of the beneficial effects of MES, its effects on individual animals and the molecular underpinnings are poorly understood and rarely studied. Here, we examined the effects of MES on individual animal and its mechanisms by mainly using Caenorhabditis elegans, a powerful genetic model organism. Interestingly, MES increased stress resistance and suppressed excess fat accumulation in wild-type N2 worms but not in AMPK/AAK-2 and LKB1/PAR-4 mutant worms. MES promoted the nuclear localization of transcription factors DAF-16 and SKN-1 and consequently increased the expression of anti-stress genes, whereas MES inhibited the nuclear localization of SBP-1 and suppressed the expression of lipogenic genes. Moreover, we found that MES induced the activation of LKB1/PAR4-AMPK/AAK2 pathway in C. elegans and in several mammalian cell lines. The mitochondrial membrane potential and cellular ATP level were slightly and transiently decreased by MES leading to the activation of LKB1-AMPK signaling pathway. Together, we firstly and genetically demonstrated that MES exerts beneficial effects such as stress resistance and suppression of excess fat accumulation, via activation of LKB1-AMPK signaling pathway.
Highlights
Endogenous and exogenous electrical current influence how proteins behave and interact with one another at cellular and organismal levels
mild electrical stimulation (MES) increased the nuclear expression of DAF-16::GFP (Fig. 1C–D) and SKN-1::GFP (Fig. 1E–F), but not heat shock factor-1 (HSF-1)::GFP (Fig. 1G–H)
Exogenous electrical stimulation has been applied as treatment modality in clinical setting for a variety of diseases with few side effects [1]
Summary
Endogenous and exogenous electrical current influence how proteins behave and interact with one another at cellular and organismal levels. Exogenous electrical stimulation has been studied using repetition frequency-, current wave form- or voltage-based condition [1]. The detailed cellular mechanisms for the positive effects of electrical stimulation remain elusive, it is thought that the beneficial effects can be attributed to the activation of signal transduction pathways [4]. We and others have reported that electrical stimulation activates PI(3)K-Akt signaling pathway resulting in wound healing and amelioration of hyperglycemia [5,6,7]. We have reported that combination treatment of mild electrical stimulation
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