Clocks in the Vasculature Essay Example | Topics and Well Written Essays - 1000 words

Clocks in the Vasculature - Essay Example An example is mammalian sleep rhythm or hunger, and its is now well known that there is a light-controlled master clock in the brain that controls these activities. Now the research is exploring the molecular mechanisms of these clocks in the peripheral tissues, which have been postulated to work through nutrient availability, although the exact mechanism is not known. heart which is essentially vascular tissue. This activity physiologically is autonomous, originating in the neurocardiac muscles of the heart and in health, occurs 72 times per minute in a regular fashion. In most and usual cases, human beings cannot control the frequency of these beats on their own. However, several neurophysiological conditions can cause change in this pattern and there is established roles of emotion, feelings, strenuous activities, stress in destabilizing this clock either to a higher or a lower rate, and there are physiological systems that tends to bring back these abnormal rates to normal through neural and humoral mechanisms. Small molecules interact with molecular hormone receptors module circadian rhythm. Catecholamines, vasoactive hormones, such as vasopressin and angiotensin interact with positive circadian regulators both centrally and at the peripheral vascular tissues to express circadian variations in heart rates, blood pressure, and vascular resistance (Harris, 2009). Genetic Mechanism Curtis et al. (2004) indicated the molecular mechanism of this clock. This occurs through pacemaker rhythms generated and sustained through positive and negative feedback loops. These in turn are mediated through transcriptional regulation at the genetic level (Curtis et al. 2004). Molecular Mechanism The drivers of this biological and molecular rhythmicity are transcriptional activation of of Per and Cry genes. These occur through transcriptional activation of feedback loop by heterodimeric bHLH-PAS proteins. It has been shown that these trascriptional coactivators and histone acetyltransferase initiate the key events in molecular rhythmicity. These, p300/CBP, PCAF, and ACTR, react with bHLH-PAS proteins, CLOCK and NPSA2, to lead to positive gene expression (Ko and Takahashi, 2006). Link to Vasculature The negative feedback loop is mediated by Cry2 mediated repression of NPAS2:BMAL1 through overexpression of p300. This leads to a circadian and time-dependent association with NPAS2 in the vasculature, which is timed in such a manner that it will precede the peak expression of the target genes (Westgate et al., 2008). Therefore, at the molecular level this is essentially a histone H3 acetylation. It has been correlated with the cyclical expression of the mRNAs