Freethought & Rationalism Archive

Principia · 01-06-2003, 08:21 PM

Biochemistry 2002 Oct 8;41(40):11941-5

Biochemical basis for the biological clock.

Morre DJ, Chueh PJ, Pletcher J, Tang X, Wu LY, Morre DM.

Quote:

NADH oxidases at the external surface of plant and animal cells (ECTO-NOX proteins) exhibit stable and recurring patterns of oscillations with potentially clock-related, entrainable, and temperature-compensated period lengths of 24 min. To determine if ECTO-NOX proteins might represent the ultradian time keepers (pacemakers) of the biological clock, COS cells were transfected with cDNAs encoding tNOX proteins having a period length of 22 min or with C575A or C558A cysteine to alanine replacements having period lengths of 36 or 42 min. Here we demonstrate that such transfectants exhibited 22, 36, or 40 to 42 h circadian patterns in the activity of glyceraldehyde-3-phosphate dehydrogenase, a common clock-regulated protein, in addition to the endogenous 24 h circadian period length. The fact that the expression of a single oscillatory ECTO-NOX protein determines the period length of a circadian biochemical marker (60 X the ECTO-NOX period length) provides compelling evidence that ECTO-NOX proteins are the biochemical ultradian drivers of the cellular biological clock.

Here is a related news article.

One particularly exciting application is noted here:

Quote:

Under investigation is a novel mechanism for the regulation of cell proliferation and surface characteristics important to loss of growth control in cancer. We have discovered a 34 kD hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity located at the external plasma membrane surface (ECTO-NOX). The constitutive activity (CNOX) normally is sensitive to stimulation or inhibition by hormones, growth factors and other effectors linked to growth through receptor-mediated transplasma membrane signaling. In cancer cells, a second activity (tNOX) is found that is constitutively activated and no longer hormone- or growth factor-responsive. Certain anticancer drugs, characterized as a class by a propensity to occupy quinone-binding sites, inhibit tNOX activities from cancer cells but not the CNOX from either cancer or non-cancer cells. When tNOX is inhibited, the cancer cells fail to enlarge following cell division and undergo programmed cell death (apoptosis) typified by characteristic nuclear and cell membrane changes.

Amit Misra · 01-09-2003, 09:49 PM

Around 1995, there was a series of Nature papers on 2 Drosophila genes called (as far as I recall) tim and per. These were shown to regulate time periods and periodicity of several biorhythms.
I'm more interested in another kind of rhythm: the periodic or episodic secretion of hormones. My pet bee-in-bonnet is the cascade of hormones in the "hypothalamus-pituitary-gonad" axis: how gonadotropin-releasing hormone (GnRH) signals the pituitary to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which then induce synthesis of testosterone (T) in the testes. T then goes and gives a negative feedback to the pituitary and hypothalamus, shutting down GnRH, LH and FSH. All three consequently decay exponentially, until T drops to a low threshold. Hypothalamus neurons then fire another burst of GnRH, and another cycle commences. There are roughly 16-20 such events everyday in the life of a man.
Check out Veldhuis et al, specially J. Clin Endocrinol Metab 65 (5): 921 for details, if you like.

Principia · 01-10-2003, 07:12 PM

Thanks Amit for the citations. The hypothalamus-pituitary-gonadal axis you mention is interesting to me because it demonstrates that negative feedback pathways are quite capable of generating stable cycles in normal physiology. Another one that I am aware of is the mechanism that generates heart rate variability, in which autoregulation of blood pressure, coupled with respiration, induces regular, periodic beat to beat variations in heart rate...

Anyway, I'll check up on tim and per.

Amit Misra · 01-12-2003, 11:06 PM

Quote:

stable cycles in normal physiology

You know, one wonders how stable these cycles are. I know nothing and follow less about fractals, but it sort of bugs me that there is a great deal of fuzziness involved in physiological Zeitgebers.
To lead on to another pompous statement, are organisms "fractals in time" much as sand-dunes and snowflakes are fractals in space?
Amit

Thread Tools	Search this Thread
Show Printable Version	Search this Thread: Advanced Search

01-09-2003, 09:49 PM	#2
Amit Misra Senior Member Join Date: Jun 2000 Location: Lucknow, UP, India Posts: 814	Around 1995, there was a series of Nature papers on 2 Drosophila genes called (as far as I recall) tim and per. These were shown to regulate time periods and periodicity of several biorhythms. I'm more interested in another kind of rhythm: the periodic or episodic secretion of hormones. My pet bee-in-bonnet is the cascade of hormones in the "hypothalamus-pituitary-gonad" axis: how gonadotropin-releasing hormone (GnRH) signals the pituitary to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH), which then induce synthesis of testosterone (T) in the testes. T then goes and gives a negative feedback to the pituitary and hypothalamus, shutting down GnRH, LH and FSH. All three consequently decay exponentially, until T drops to a low threshold. Hypothalamus neurons then fire another burst of GnRH, and another cycle commences. There are roughly 16-20 such events everyday in the life of a man. Check out Veldhuis et al, specially J. Clin Endocrinol Metab 65 (5): 921 for details, if you like.

01-10-2003, 07:12 PM	#3
Principia Veteran Member Join Date: Mar 2002 Location: anywhere Posts: 1,976	Thanks Amit for the citations. The hypothalamus-pituitary-gonadal axis you mention is interesting to me because it demonstrates that negative feedback pathways are quite capable of generating stable cycles in normal physiology. Another one that I am aware of is the mechanism that generates heart rate variability, in which autoregulation of blood pressure, coupled with respiration, induces regular, periodic beat to beat variations in heart rate... Anyway, I'll check up on tim and per.

Freethought & Rationalism Archive

The archives are read only.