Extracellular Vesicles: Potential Participants in Circadian Rhythm Synchronization

Abstract

The circadian rhythm (CR) is a set of autonomous endogenous oscillators. Exposure to the 24-hour day-night cycle synchronizes our CR system, maintaining homeostasis and human health. Several mechanisms for the CR system have been proposed, including those underlying the function (transcriptional-translational negative-feedback loops, or TTFLs), mechanisms regulating the TTFLs, and the mechanism by which the “server clock” is synchronized to environmental time. Several pathways downstream of the “server clock” perform well-characterized biological functions. However, the synchronization between the “server clock” (the endogenous master clock seated in the suprachiasmatic nucleus within the hypothalamus) and the “client clock” (imbedded in nearly every cell in the form of interlocking TTFLs) is difficult to explain with current theories. Extracellular vesicles (EVs), which are involved in intercellular communication and have recently been found to participate in regulation of the “client clock”, might be the answer to this question. In this review, we summarize the current knowledge of CRs, TTFLs, and EVs, examine research findings about the functions of EVs in the CR system, and discuss the issues requiring attention in future research.

The importance of determining circadian parameters in pharmacological studies

“…These are then transmitted to local clocks in the brain and to peripheral clocks (Dibner, Schibler, & Albrecht, 2010), via direct output pathways such as synaptic communication, gap junctions, and hormone secretion (Ramkisoensing & Meijer, 2015;Welsh, Takahashi, & Kay, 2010). In addition, communication via extracellular vesicles may also contribute to the temporal regulation of the system (Tao & Guo, 2018). The SCN is, thus, responsible for coordinating all clocks within the body (Albrecht, 2012).…”

EWSAT1 Acts in Concert with Exosomes in Osteosarcoma Progression and Tumor‐Induced Angiogenesis: The “Double Stacking Effect”

“…The results showed that the Exos were 73.18 ± 34.49 nm in diameter, which is consistent with the definition of Exos. [ 18,34 ] Western blotting (Figure 4C) was used to detect the most accepted surface markers (CD63, CD81, and CD9) of Exos, and the results confirmed Exos identity. In addition, PAGE was used to determine EWSAT1 levels in NC‐Exos, KRas‐KO‐Exos, and EWSAT1‐KD‐Exos; EWSAT1 level in EWSAT1‐KD‐Exos was significantly reduced, while no similar changes were observed in KRas‐KO‐Exos (Figure 4C).…”

“…Transmission electron microscopy ( Figure 4 A) shows that the Exos were isolated and were vesicle‐shaped, with diameter ranging from 30 to 100 nm, which is consistent with the accepted definition of Exos. [ 18,34 ] The size distribution (Figure 4B) of Exos was measured using dynamic light scattering with Nanosizer technology. The results showed that the Exos were 73.18 ± 34.49 nm in diameter, which is consistent with the definition of Exos.…”

“…Exos research has had its ups and downs. [ 34b,41 ] Initially, Exos were considered cell waste disposal bodies. [ 34b,41 ] However, later, the other important functions of Exos were identified, which assisted in understanding many hitherto unexplained biological paradoxes.…”

Changing the tone of clinical study design in the cannabis industry

“…The principal region of the brain that coordinates the 24-hour biological rhythmicity is the suprachiasmatic nucleus (SCN) located in the hypothalamus [9]. The endogenous circadian rhythm consists of the master/server clock seated in the SCN and the subordinate/client clock which is embedded in nearly every cell in the form of interlocking transcriptional-translational negative-feedback loops made up of Clock genes that exert their biological effects via Clock-controlled genes [10]. At the genetic level, heterodimerization of brain and muscle Arnt-like 1 (BMAL1) with Clock or neuronal PAS domain protein 2 (NPAS2) activates the translation of the PER and CRY dosing [24].…”