Kim TD, etal., Genes Dev. 2007 Apr 1;21(7):797-810.
The circadian rhythm of pineal melatonin requires the nocturnal increment of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase [AANAT]) protein. To date, only limited information is available in the critical issue of how AANAT
:700;'>AANAT protein expression is up-regulated exclusively at night regardless of its species-specific mRNA profiles. Here we show that the circadian timing of AANAT protein expression is regulated by rhythmic translation of AANAT mRNA. This rhythmic control is mediated by both a highly conserved IRES (internal ribosome entry site) element within the AANAT 5' untranslated region and its partner hnRNP Q (heterogeneous nuclear ribonucleoprotein Q) with a peak in the middle of the night. Consistent with the enhancing role of hnRNP Q in AANAT IRES activities, knockdown of the hnRNP Q level elicited a dramatic decrease of peak amplitude in the AANAT protein profile parallel to reduced melatonin production in pinealocytes. This translational regulation of AANAT mRNA provides a novel aspect for achieving the circadian rhythmicity of vertebrate melatonin.
Falcón J, etal., Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):314-9. doi: 10.1073/pnas.1312634110. Epub 2013 Dec 18.
Melatonin (N-acetyl-5-methoxytrypamine) is the vertebrate hormone of the night: circulating levels at night are markedly higher than day levels. This increase is driven by precisely regulated increases in acetylation of serotonin in the pineal gland by arylalkylamine N-acetyltransferase (AANAT
='font-weight:700;'>AANAT), the penultimate enzyme in the synthesis of melatonin. This unique essential role of AANAT in vertebrate timekeeping is recognized by the moniker the timezyme. AANAT is also found in the retina, where melatonin is thought to play a paracrine role. Here, we focused on the evolution of AANAT in early vertebrates. AANATs from Agnathans (lamprey) and Chondrichthyes (catshark and elephant shark) were cloned, and it was found that pineal glands and retinas from these groups express a form of AANAT that is compositionally, biochemically, and kinetically similar to AANATs found in bony vertebrates (VT-AANAT). Examination of the available genomes indicates that VT-AANAT is absent from other forms of life, including the Cephalochordate amphioxus. Phylogenetic analysis and evolutionary rate estimation indicate that VT-AANAT evolved from the nonvertebrate form of AANAT after the Cephalochordate-Vertebrate split over one-half billion years ago. The emergence of VT-AANAT apparently involved a dramatic acceleration of evolution that accompanied neofunctionalization after a duplication of the nonvertebrate AANAT gene. This scenario is consistent with the hypotheses that the advent of VT-AANAT contributed to the evolution of the pineal gland and lateral eyes from a common ancestral photodetector and that it was not a posthoc recruitment.
The transient receptor potential melastatin-8 (TRPM8) is a cold and menthol receptor located in the sensory ganglia. Immunohistochemistry for TRPM8 was performed on oral and craniofacial structures of the rat. TRPM8-immunoreactive (-IR) nerve fibers were detected in the oral mucous membrane. In the
gingiva, TRPM8-IR nerve fibers were abundant beneath and within crestal and outer epithelia. Such nerve fibers were also common beneath and within taste buds in the incisive papilla. In addition, TRPM8-immunoreactivity was expressed by some taste bud cells in the papilla. Lips, periodontal ligaments and salivary glands as well as masticatory muscles and temporomandibular joints were mostly devoid of TRPM8-IR nerve fibers. A double immunofluorescence study indicated different distribution patterns of nerve fibers containing TRPM8 and calcitonin gene-related peptide in oral and craniofacial tissues. Retrograde tracing method also indicated that TRPM8-IR nerve fibers in the gingiva and incisive papilla originate from small sensory neurons in the trigeminal ganglion. TRPM8 may be associated with cool, cold nociceptive (
Li S and Pan Y, Ann Anat. 2018 Mar;216:52-59. doi: 10.1016/j.aanat.2017.10.005. Epub 2017 Nov 22.
Connective tissue growth factor (CTGF) is a downstream mediator of transforming growth factor-beta 1 (TGF-β1) and TGF-β1-induced CTGF expression is regulated through SMAD pathway. However, there is no literature showing the expression of TGF-β1-SMAD2/3-CTGF signaling pathway during postnatal tooth d
evelopment and the formation of junctional epithelium (JE). Hence, we aimed to analyze the localization of TGF-β1, CTGF and phosphorylated SMAD2/3 (p-SMAD2/3) in the developing postnatal rat molars. Wistar rats were killed at postnatal (PN) 0.5, 3.5, 7, 14 and 21days and the upper jaws were processed for immunohistochemistry. At PN0.5 and PN3.5, weak staining for TGF-β1 and CTGF was evident in preameloblasts (PA), while moderate to strong staining was seen in odontoblasts (OD), dental papilla (DPL), secretary ameloblasts (SA), preodontoblasts (PO) and polarized odontoblasts (PoO). There was no staining for p-SMAD2/3 in PA, SA, PO and PoO, although strong staining was localized in DPL. OD was initially moderately positive and then negative for p-SMAD2/3. At PN7, intense staining for TGF-β1 and CTGF was observed in SA, OD, dental pulp (DP) and predentin respectively. p-SMAD2/3 was strongly expressed in DP and moderately expressed in SA and OD. At PN14 and PN21, both reduced enamel epithelium (REE) and JE showed a strong reaction for TGF-β1 and CTGF. p-SMAD2/3 was intensely and weakly expressed in REE and JE respectively. These data demonstrate that the expression of CTGF, TGF-β1 and p-SNAD2/3 is tissue-specific and stage-specific, and indicate a regulatory role for a TGF-β1-SMAD2/3-CTGF signaling pathway in amelogenesis, dentinogenesis and formation of JE.
Jeremy M, etal., Ann Anat. 2017 May;211:46-54. doi: 10.1016/j.aanat.2017.01.009. Epub 2017 Feb 3.
Aging is a complex irreversible process which leads to decline in body physiology including reproductive activity. Neurological and brain functions defects have been studied in the d-gal induced aging rodent model. However, there is dearth of literature on reproductive aging induced by d-gal treatme
nt. Visfatin is an adipokine which regulates testicular steroidogenesis and its level increases under stress conditions to cope and extend longevity. To the best of our knowledge the expression and localization pattern of visfatin and histological evaluation of d-gal induced aged testis have not been investigated. Thus, we hypothesized that the expression pattern and histoarchitecture of d-gal induced aged testis are impaired. Therefore, the aim of the present study was to elucidate the histopthological, immunohistochemical localization and expression of visfatin in d-gal induced aged testis along with serum testosterone level, sperm count and daily sperm production. The western blot and immunohistochemical results of the present study showed that d-gal treatment decreases visfatin expression in the testis, particularly in the Leydig cell, and decreases serum testosterone level. Further, d-gal treatment decrease in testosterone levels was positively correlated with decreases in Johnsen's score, mean seminiferous tubule diameter, germinal epithelium height, sperm count and daily sperm production. The multinucleated giant cells showed strong immunostaining for visfatin and suggest the role of visfatin as pro/anti-apoptotic factor. Thus, it can be suggested that visfatin may play an important role in testicular aging by regulating testicular steroidogenesis and spermatogenesis.
Romer P, etal., Ann Anat. 2010 Aug 20;192(4):205-9. doi: 10.1016/j.aanat.2010.05.006. Epub 2010 Jun 11.
The spheno-occipital synchondrosis is part of the cranial base growth plate and is of crucial importance in craniofacial development. In this investigation, we studied changes in collagen gene expression in the spheno-occipital synchondrosis in order to identify the developmental stages most importa
nt for extracellular matrix production and ossification of the rat cranial base growth plate. Gene transcripts of type II and X collagen were most abundant at day 10 postnatally in the spheno-occipital synchondrosis. This observation is assumed to be due to intrinsic genetic factors and local environmental factors.
Martins FF, etal., Ann Anat. 2017 Mar;210:44-51. doi: 10.1016/j.aanat.2016.11.013. Epub 2016 Dec 13.
Brown adipose tissue (BAT) is specialized in heat production, but its metabolism in ob/ob mice is still a matter of debate. We aimed to verify ob/ob mice BAT using C57Bl/6 male mice (as the wild-type, WT) and leptin-deficient ob/ob mice (on the C57Bl/6 background strain), at three months of age (n=1
0/group). At euthanasia, animals had their interscapular BAT weighed, and prepared for analysis (Western blot, and RT-qPCR). In comparison with the WT group, the ob/ob group showed reduced thermogenic signaling markers (gene expression of beta 3-adrenergic receptor, beta3-AR; PPARgamma coactivator 1 alpha, PGC1alpha, and uncoupling protein 1, UCP1). The ob/ob group also showed impaired gene expression for lipid utilization (perilipin was increased, while other markers were diminished: carnitine palmitoyltransferase-1b, CPT-1b; cluster of differentiation 36, CD36; fatty acid binding protein 4, FABP4; fatty acid synthase, FAS, and sterol regulatory element-binding protein 1c, SREBP1c), and altered protein expression of insulin signaling (diminished pAKT, TC10, and GLUT-4). Lastly, the ob/ob group showed increased gene expression of markers of inflammation (interleukin 1 beta, IL-1beta; IL-6, tumor necrosis factor alpha, TNFalpha; and monocyte chemotactic protein-1, MCP-1). In conclusion, the ob/ob mice have decreased thermogenic markers associated with reduced gene expression related to fatty acid synthesis, mobilization, and oxidation. There were also alterations in insulin signaling and protein and gene expressions of inflammation. The findings suggest that the lack of substrate for thermogenesis and the local inflammation negatively regulated thermogenic signaling in the ob/ob mice.
