PubMed · 14926932
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A B DROOGLEEVER FORTUYN. 1952-01-10. [Lenz's method].. https://pubmed.ncbi.nlm.nih.gov/14926932/
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The genes encoding enzymes of the tyrosinase family are strong candidates for coat color variation in mammals. To investigate their influence in domestic cat coat color, we determined the complete nucleotide coding sequence of the domestic cat genes tyrosinase (TYR)--a plausible candidate gene for the albino (C) locus, and tyrosinase related protein 1 (TYRP1)--a candidate gene for the brown (B) locus. Sequence variants between individuals exhibiting variation in pigmentation were submitted to association studies. In TYR, two nonsynonymous substitutions encoding TYR-G301R and TYR-G227W were associated with the siamese and burmese phenotypes of the albino locus, respectively. TYRP1 was mapped on chromosome D4 within 5 cM of a highly polymorphic microsatellite, previously found to be fixed in a cat breed selected for the chocolate (b) allele of the B locus, which reinforced TYRP1 as a candidate gene for the B locus in the domestic cat. Two DNA polymorphisms, one leading to a TYRP1-A3G substitution in the signal peptide and another to an in-frame insertion TYRP1-421ins17/18 caused by a donor splice site mutation in intron 6, were associated with the chocolate (b) allele. A premature UAG stop codon at position 100 of TYRP1 was associated with a second allele of the B locus, cinnamon (b(l)). The results provide very strong evidence that the specific nucleotide variants of feline TYR (chromosome D1) are causative of the siamese (c(s)) and burmese (c(b)) alleles of the albino locus, as well as nucleotide variants of TYRP1 (chromosome D4) as specifying the chocolate (b) and cinnamon (b(l)) alleles of the B locus.
Apigenin (4',5,7-trihydroxyflavone), a flavone subclass of flavonoid widely distributed in many herbs, fruits, and vegetables is a substantial component of the human diet and has been shown to possess a variety of biological activities including tumor growth inhibition and chemoprevention. Recent studies in several biological systems have shown that apigenin induces tumor growth inhibition, cell cycle arrest, and apoptosis. Free radical-induced degradation of polyunsaturated fatty acid results in electrophilic products and causes severe oxidative stress. Oxidative stress induced by free radicals, nonoxidizing species, electrophiles, and associated DNA damages have been frequently coupled with carcinogenesis. In the present study, the protective role of apigenin was examined against the oxidative stress caused by N-nitrosodiethylamine (NDEA) and phenobarbital (PB) in Wistar albino rats. Oxidative stress was measured in terms of lipid peroxidation (LPO) and protein carbonyl formation. Oxidative stress-induced DNA damage was measured by single cell gel electrophoresis (comet assay). Apigenin exhibited its antioxidant defense against NDEA-induced oxidative stress. We have observed minimal levels of LPO and DNA damage in apigenin-treated hepatoma bearing animals. Based on the results, we suggest that apigenin may be developed as a promising chemotherapeutic agent against the development of chemical carcinogenesis.
This paper provides a critical review of the numerous and various biological functions so far attributed to neuromelanin and an attempt to provide a unified theory based on the peculiar physical and chemical properties of the black particle (the neuromelanin cage). It is stressed that neuromelanin is not homogeneous, as is commonly accepted, but is made up of different substrate specific black pigments formed by the oxidation of o.diphenols or other oxygenated precursors (substantia nigra melanin, locus coeruleus melanin, retinal pigmented epithelium or ocular melanin, inner-ear melanin, and so on). Ocular melanin is believed to protect the eye by trapping metals and free radicals. The paper shows that this unconfirmed mechanism is a rather fortuitous irreversible molecular accident, which at times may prove itself deleterious. Albinism often leads to deafness in animals, indicating a genetic correlation. These two conditions appear to be correlated at a molecular level to eye/ear pigmentation and suggest verifying this hypothesis in normal and albino human individuals. Skin and ocular melanin are chemically different. However, they are both involved in light absorption/dissipation. The black particle structure (melanin cage) is believed to be fundamental to this process because there is a common bioelectric mechanism. The latter is worth of further investigation. It is also proposed checking how ocular melanin dissipates the excessive absorbed light (as heat or as current?). It has been claimed that inner-ear melanin mutes acoustic waves. This paper suggests investigating the underlying mechanism and also studying whether this pigment is bio-electrically involved in audiology. According to numerous authors, substantia nigra melanin is only biological garbage. This view is rejected, and it is stressed that intracellular melanogenesis is a fundamental and genetically controlled physiological process. It has been repeatedly claimed that the binding of iron, heavy metals, free radicals and harmful chemicals by substantia nigra melanin is fundamental to body detoxification/protection. Presumably, such irreversible and generic binding mechanisms have no physiological foundation; it is suggested the alternative that, substantia nigra melanin acts as semiconductor, transmitting and modulating nervous impulses, in a reversible way. In fact, substantia nigra melanin is absent or significantly scarce in two conditions of life in which the coordination of movement is either inefficient (newborn babies) or strongly compromised (Parkinson). To check this assumption, further investigation of nucleus caudatus, putamen, globus pallidus, substantia nigra pars compacta and reticulata, nucleus hypothalamicus is recommended.