The Suppression of Pineal Melatonin Content and<i>N</i>-AcetyItransferase Activity by Different Light Irradiances in the Syrian Hamster: A Dose-Response Relationship<sup>*</sup>

Brainard, George C.; Richardson, Bruce A.; King, Thomas S.; Matthews, Susan A.; Reíter, Russel J.

doi:10.1210/endo-113-1-293

Cited by 134 publications

(61 citation statements)

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“…In both rodents and humans, light exposure suppresses pineal melatonin production in an intensity-, wavelength-, and duration-dependent manner (20,21,52). The present results represent the first demonstration that the rates of both rat hepatoma and human breast cancer growth increase as a function of a light intensity-dependent suppression of nocturnal circulating melatonin levels.…”

Section: Discussionsupporting

confidence: 54%

“…Groups of tumor-bearing rats were housed in light exposure chambers that contained two separate solid-state, electromagnetic fluorescent ballasts with rapid-start, cool-white lamps connected to separate 24-hour timers and separated by a metal baffle (20). One ballast/lamp system (GE Watt-Miser, F34CW-RS-WM, 34-W bulb) in each chamber was set up to provide a direct, steady, bright light stimulus (345 AW/cm 2 ) at the animals' eye level during the light portion of a 12-hour light/12-hour dark cycle.…”

Section: Methodsmentioning

confidence: 99%

“…The duration of melatonin production during the night is directly proportional to the length of the dark period (17)(18)(19). The alternating light/dark cycle entrains circadian melatonin production to a 24-hour cycle, whereas ocular exposure to light during darkness rapidly suppresses melatonin production depending on the intensity, wavelength, and duration of the light exposure (20,21). In experimental systems, melatonin plays a fundamental role in the regulation of seasonal reproduction, circadian rhythm activity, retinal physiology, cardiovascular effects, immune function, and cancer (17)(18)(19).…”

Section: Introductionmentioning

confidence: 99%

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Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats

et al. 2005

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The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Exposure of rats bearing rat hepatomas or human breast cancer xenografts to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 MW/cm 2 ) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 MW/cm 2 (i.e., 2,800 lx). Compared with tumors perfused with daytimecollected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers. (Cancer Res 2005; 65(23): 11174-84)

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Section: Discussionsupporting

confidence: 54%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats

et al. 2005

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“…It will be important to test for a full fluence-response curve at 420 nm to (1) clarify the precise sensitivity of the melatonin system to this wavelength and (2) determine if this wavelength is univariant with the fluence-response curves of the other eight wavelengths. Previous studies with animals and humans have illustrated similar fluence-response relationships for melatonin suppression and other circadian responses with monochromatic and broadspectrum light (Brainard et al, 1983(Brainard et al, , 1988Podolin et al, 1987;McIntyre et al, 1989;Nelson and Takahashi, 1991;DkhissiBenyahya et al, 2000;Zeitzer et al, 2000). The initial attempts to define circadian and neuroendocrine responses to photons of different wavelengths began with polychromatic action spectra, which tested single irradiances of broader light bandwidths in various rodent species.…”

Section: Discussionmentioning

confidence: 97%

Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor

et al. 2001

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The photopigment in the human eye that transduces light for circadian and neuroendocrine regulation, is unknown. The aim of this study was to establish an action spectrum for lightinduced melatonin suppression that could help elucidate the ocular photoreceptor system for regulating the human pineal gland. Subjects (37 females, 35 males, mean age of 24.5 Ϯ 0.3 years) were healthy and had normal color vision. Full-field, monochromatic light exposures took place between 2:00 and 3:30 A.M. while subjects' pupils were dilated. Blood samples collected before and after light exposures were quantified for melatonin. Each subject was tested with at least seven different irradiances of one wavelength with a minimum of 1 week between each nighttime exposure. Nighttime melatonin suppression tests (n ϭ 627) were completed with wavelengths from 420 to 600 nm. The data were fit to eight univariant, sigmoidal fluence-response curves (R 2 ϭ 0.81-0.95). The action spectrum constructed from these data fit an opsin template (R 2 ϭ 0.91), which identifies 446-477 nm as the most potent wavelength region providing circadian input for regulating melatonin secretion. The results suggest that, in humans, a single photopigment may be primarily responsible for melatonin suppression, and its peak absorbance appears to be distinct from that of rod and cone cell photopigments for vision. The data also suggest that this new photopigment is retinaldehyde based. These findings suggest that there is a novel opsin photopigment in the human eye that mediates circadian photoreception.

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“…Furthermore, the specific localization of acetylating activity that others have described does not mirror the distribution of the opioid peptides, suggesting that these endogenous opioid peptides may not be the natural substrates for the brain acetylating enzyme (29). Since this enzyme clone was isolated from a cDNA library derived from rat brain, it will be particularly relevant to analyze the substrate specificity of the recombinant and natural enzyme (15) with regard to histones (11), serotonin (30,31), and a-MSH, which has been shown to be O-acetylated as well as a-N-acetylated in some tissues (28,32). Additionally, the difference in rate of acetylation of isoniazid and other drugs is probably due to differences in the amount or type of acetyltransferase (33).…”

Section: Resultsmentioning

confidence: 99%

Isolation of enzyme cDNA clones by enzyme immunodetection assay: isolation of a peptide acetyltransferase.

Eberwine¹,

Barchas²,

Hewlett³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

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The biological activity of many proteins and peptides can be profoundly affected by enzyme-catalyzed covalent modifications such as acetylation, sulfation, glycosylation, or amidation. This article describes the cloning of such an enzyme, a peptide acetyltransferase from rat brain that catalyzes the amino-terminal acetylation of endorphins and perhaps other substrates in vivo. Blot-hybridization analysis suggests that the mRNA encoding the acetyltransferase is P2.0 kilobases, is present in whole rat brain and rat hypothalamus, and is slightly larger in mouse AtT20 tumor cells. The acetyltransferase was cloned by using a strategy whereby a cDNA expression library was screened with a solid-phase enzyme-activity assay; this technique combines the use of the substrate coupled to a solid support and subsequent recognition of the product by using a specific antiserum. We have called this method the enzyme immunodetection assay (EIDA). The EIDA should prove useful in the isolation of other clones for proteins that possess enzymatic activity upon expression in bacterial hosts.Amino-terminal acetylation is a physiologically important posttranslational modification that can modulate the bioactivity of a number of molecules. Both a-melanotropin (a-MSH) and 8-endorphin, which are derived from the same precursor protein, proopiomelanocortin (1), are acetylated at the amino terminus in melanotrophs of the rat intermediate pituitary gland (2-4). However, the P-endorphin in human adrenal anterior-lobe corticotrophs and in brain is predominantly the nonacetylated species (5-7). Whereas unmodified ,B-endorphin is a potent opioid peptide, the acetylated species does not bind to opioid receptors and, consequently, cannot elicit a physiological response (8, 9). In contrast, acetylation can enhance biological activity, as evidenced by a-MSH, which is a considerably more potent melanocyte-stimulating hormone in vivo than is the nonacetylated derivative (10).Aside from a potential role in the regulation of the activity of peptide hormones, acetylation is also a common modification of histone proteins (11). The degree of histone acetylation has been shown to alter the ability of some histones to bind to DNA, leading to speculation that acetylation plays a role in the regulation of gene transcription (12).Acetylation is clearly an important covalent modification of peptides and proteins, yet little is known about the cellular localization or regulation of the enzyme(s) catalyzing aminoterminal acetylation. An understanding of the enzyme would be greatly enhanced by the availability of antibodies and cDNA clones, allowing the measurement of protein and mRNA levels. With these tools, the important question of whether coregulation occurs between a substrate (proopiomelanocortin) and one of its processing enzymes can be addressed. In view of these goals, the cloning of cDNA encoding an acetyltransferase activity was initiated. MATERIALS AND METHODSPreparation of Substrate Paper. Aminophenyl thioether paper (APT) (13) was cut to fit 1...

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The Suppression of Pineal Melatonin Content andN-AcetyItransferase Activity by Different Light Irradiances in the Syrian Hamster: A Dose-Response Relationship^*

Cited by 134 publications

References 13 publications

Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats

Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats

Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor

Isolation of enzyme cDNA clones by enzyme immunodetection assay: isolation of a peptide acetyltransferase.

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The Suppression of Pineal Melatonin Content andN-AcetyItransferase Activity by Different Light Irradiances in the Syrian Hamster: A Dose-Response Relationship*

Cited by 134 publications

References 13 publications

Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats

Melatonin-Depleted Blood from Premenopausal Women Exposed to Light at Night Stimulates Growth of Human Breast Cancer Xenografts in Nude Rats

Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor

Isolation of enzyme cDNA clones by enzyme immunodetection assay: isolation of a peptide acetyltransferase.

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The Suppression of Pineal Melatonin Content andN-AcetyItransferase Activity by Different Light Irradiances in the Syrian Hamster: A Dose-Response Relationship^*