{"title":"Rab35 Targeting to the Plasma Membrane Is Dependent on the C-terminal Polybasic Cluster.","authors":"Katsuhisa Kawai, Youhei Egami, Arata Nishigaki, Nobukazu Araki","doi":"10.1267/ahc.20-00006","DOIUrl":"https://doi.org/10.1267/ahc.20-00006","url":null,"abstract":"<p><p>Rab35, a member of the Rab GTPase family, has been implicated in various cellular processes including cell motility and membrane trafficking. Although Rab35 is localized to the plasma membrane, Rab proteins that are identified to have high sequence homology with Rab35 exhibit distinct subcellular localization patterns. Comparing the amino acid sequences between Rab35 and its family members revealed a significant variation in an approximate 30-amino acid region of the C-terminus. This suggests that this region determines the subcellular localization of individual Rab proteins. To confirm this hypothesis, we constructed Rab35-Rab10 chimera proteins by exchanging their C-terminal domains with one another. Confocal microscopy of RAW264 cells expressing EGFP-fused Rab35-Rab10 chimeras has indicated that the C-terminal region of Rab35 is critical for its plasma membrane localization. Furthermore, we were able to determine that a basic amino acid cluster exists in the C-terminal region of Rab35 and that Rab35 localization shifts to the Golgi membrane when the number of basic amino acids in this region is reduced. Thus, it is likely that the approximate 30-amino acid C-terminal region containing basic clusters is responsible for Rab35 plasma membrane localization and that its preferential localization depends on the number of basic amino acids.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"53 4","pages":"93-97"},"PeriodicalIF":2.4,"publicationDate":"2020-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7450177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38334858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nuraly S Akimbekov, Ilya Digel, Dinara K Sherelkhan, Afzalunnessa B Lutfor, Mohammed S Razzaque
{"title":"Vitamin D and the Host-Gut Microbiome: A Brief Overview.","authors":"Nuraly S Akimbekov, Ilya Digel, Dinara K Sherelkhan, Afzalunnessa B Lutfor, Mohammed S Razzaque","doi":"10.1267/ahc.20011","DOIUrl":"10.1267/ahc.20011","url":null,"abstract":"<p><p>There is a growing body of evidence for the effects of vitamin D on intestinal host-microbiome interactions related to gut dysbiosis and bowel inflammation. This brief review highlights the potential links between vitamin D and gut health, emphasizing the role of vitamin D in microbiological and immunological mechanisms of inflammatory bowel diseases. A comprehensive literature search was carried out in PubMed and Google Scholar using combinations of keywords \"vitamin D,\" \"intestines,\" \"gut microflora,\" \"bowel inflammation\". Only articles published in English and related to the study topic are included in the review. We discuss how vitamin D (a) modulates intestinal microbiome function, (b) controls antimicrobial peptide expression, and (c) has a protective effect on epithelial barriers in the gut mucosa. Vitamin D and its nuclear receptor (VDR) regulate intestinal barrier integrity, and control innate and adaptive immunity in the gut. Metabolites from the gut microbiota may also regulate expression of VDR, while vitamin D may influence the gut microbiota and exert anti-inflammatory and immune-modulating effects. The underlying mechanism of vitamin D in the pathogenesis of bowel diseases is not fully understood, but maintaining an optimal vitamin D status appears to be beneficial for gut health. Future studies will shed light on the molecular mechanisms through which vitamin D and VDR interactions affect intestinal mucosal immunity, pathogen invasion, symbiont colonization, and antimicrobial peptide expression.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"53 3","pages":"33-42"},"PeriodicalIF":2.4,"publicationDate":"2020-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38120568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Differential Localization and Invasion of Tumor Cells in Mouse Models of Human and Murine Leukemias.","authors":"Kiyomi Mashima, Morio Azuma, Ken Fujiwara, Takashi Inagaki, Iekuni Oh, Takashi Ikeda, Kento Umino, Hirofumi Nakano, Kaoru Morita, Kazuya Sato, Daisuke Minakata, Ryoko Yamasaki, Masahiro Ashizawa, Chihiro Yamamoto, Shin-Ichiro Fujiwara, Kaoru Hatano, Ken Ohmine, Kazuo Muroi, Nobuhiko Ohno, Yoshinobu Kanda","doi":"10.1267/ahc.19035","DOIUrl":"https://doi.org/10.1267/ahc.19035","url":null,"abstract":"<p><p>Leukemias are refractory hematopoietic malignancies, for which the development of new therapeutic agents requires <i>in vivo</i> studies using tumor-bearing mouse models. Although several organs are commonly examined in such studies to evaluate the disease course, the effectiveness of interventions and the localization of tumor cells in the affected organs are still unclear. In this study, we histologically examined the distribution of leukemia cells in several organs using two leukemic mouse models produced by the administration of two cell lines (THP-1, a human myelomonocytic leukemia, and A20, a mouse B cell leukemia/lymphoma) to severe immunodeficient mice. Survival of the mice depended on the tumor burden. Although A20 and THP-1 tumor cells massively infiltrated the parenchyma of the liver and spleen at 21 days after transplantation, A20 cells were hardly found in connective tissues in Glisson's capsule in the liver as compared with THP-1 cells. In the bone marrow, there was more severe infiltration of A20 cells than THP-1 cells. THP-1 and A20 cells were widely spread in the lungs, but were rarely observed in the small intestine. These findings suggest that each leukemia model has a unique localization of tumor cells in several affected organs, which could critically affect the disease course and the efficacy of therapeutic agents, including cellular immunotherapies.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"53 3","pages":"43-53"},"PeriodicalIF":2.4,"publicationDate":"2020-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38120569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunohistochemical Pharmacokinetics of the Anti-diabetes Drug Alogliptin in Rat Kidney and Liver.","authors":"Yutaro Yamamoto, Yuta Yamamoto, Tetsuya Saita, Daisuke Hira, Takahito Chijiwa, Masashi Shin","doi":"10.1267/ahc.19036","DOIUrl":"10.1267/ahc.19036","url":null,"abstract":"<p><p>Alogliptin is one of a new class of therapeutic agents for type 2 diabetes called dipeptidyl peptidase-4 inhibitors. Here, we used immunohistochemistry to investigate the pharmacokinetics of alogliptin at the cell and tissue levels in the rat kidney and liver. One hour after alogliptin administration, the most noticeable immunoreactivity in the kidney was a moderate-to-strong staining in proximal tubule S3 segment epithelial cells. On the other hand, immunostaining was found only in the microvilli of S1 and S2 segment cells. Immunoreactivity was also observed in the glomerulus and distal tubules. Positive cells and almost negative cells coexisted in the collecting ducts. Twenty-four hours after administration, moderate immunostaining remained in the S3 segment but staining in other regions had almost disappeared. In the liver 1 hr after administration, hepatocyte staining differed in the hepatic lobule, with zone III being stronger than zone I. Immunostaining had almost disappeared 24 hr after administration. These findings suggest that alogliptin reabsorption at the kidney and uptake at the hepatocyte vary from region to region and that one or more types of transporter are involved in these processes. In addition, long-term alogliptin use may cause the drug to accumulate in S3 segment, leading to adverse events.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"53 3","pages":"55-60"},"PeriodicalIF":1.6,"publicationDate":"2020-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38118483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Investigation of Novel c-Kit-expressing Smooth Muscle Cells in Murine Cecum.","authors":"Satoshi Iino, Kazuhide Horiguchi, Satomi Horiguchi","doi":"10.1267/ahc.20003","DOIUrl":"https://doi.org/10.1267/ahc.20003","url":null,"abstract":"<p><p>In the gastrointestinal tract musculatures, c-Kit receptor tyrosine kinase is specifically expressed in interstitial cells of Cajal (ICC). ICC are distributed among the smooth muscle cells and are either bipolar or multipolar in shape. Our previous and current study shows that c-Kit-immunopositive smooth muscle cells are present in the murine cecum. Here, we found that c-Kit-expressing smooth muscle cells (named Kit-SM cells) are situated at the submucosal surface of the circular muscle layer. These cells showed smooth muscle actin and myosin immunoreactivities and ultrastructural features such as thick and thin filaments and caveolae. Kit-SM cells also expressed TMEM16A and LRIG1, which are known to be expressed in ICC. Although the functional significance of Kit-SM cells has yet to be revealed, these cells can be considered to have proliferation or differentiation potential in the cecal musculature.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"53 2","pages":"11-19"},"PeriodicalIF":2.4,"publicationDate":"2020-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.20003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37937450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New Insights into the Pathogenesis of Diabetic Nephropathy: Proximal Renal Tubules Are Primary Target of Oxidative Stress in Diabetic Kidney.","authors":"Ryuma Haraguchi, Yukihiro Kohara, Kanako Matsubayashi, Riko Kitazawa, Sohei Kitazawa","doi":"10.1267/ahc.20008","DOIUrl":"https://doi.org/10.1267/ahc.20008","url":null,"abstract":"<p><p>Diabetic nephropathy is a major source of end-stage renal failure, affecting about one-third cases of diabetes mellitus. It has long been accepted that diabetic nephropathy is mainly characterized by glomerular defects, while clinical observations have implied that renal tubular damage is closely linked to kidney dysfunction at the early stages of diabetic nephropathy. In this study, we conducted pathohistological analyses focusing on renal tubular lesions in the early-stage diabetic kidney with the use of a streptozotocin (STZ)-induced diabetes mellitus mouse model. The results revealed that histological alterations in renal tubules, shown by a vacuolar nucleic structure, accumulations of PAS-positive substance, and accelerated restoration stress, occur initially without the presence of glomerular lesions in the early-stage diabetic kidney, and that these tubular defects are localized mainly in proximal renal tubules. Moreover, enhanced expression of RAGE, suggesting an aberrant activation of AGEs-RAGE signaling pathway, and accumulation of oxidative modified mitochondria through the impaired autophagy/lysosome system, were also seen in the damaged diabetic proximal renal tubules. Our findings indicate that proximal tubular defects are the initial pathological events increasingly linked to the progression of diabetic nephropathy, and that controlling renal tubular damage could be an effective therapeutic strategy for the clinical treatment of diabetic nephropathy.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"53 2","pages":"21-31"},"PeriodicalIF":2.4,"publicationDate":"2020-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.20008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37936912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kenta Masui, Mio Harachi, Webster K Cavenee, Paul S Mischel, Noriyuki Shibata
{"title":"Codependency of Metabolism and Epigenetics Drives Cancer Progression: A Review.","authors":"Kenta Masui, Mio Harachi, Webster K Cavenee, Paul S Mischel, Noriyuki Shibata","doi":"10.1267/ahc.20002","DOIUrl":"10.1267/ahc.20002","url":null,"abstract":"<p><p>Cancer is widely considered to be a set of genetic diseases that are currently classified by tissue and cell type of origin and, increasingly, by its molecular characteristics. This latter aspect is based primarily upon oncogene gains, tumor suppressor losses, and associated transcriptional profiles. However, cancers are also characterized by profound alterations in cellular metabolism and epigenetic landscape. It is particularly noteworthy that cancer-causing genomic defects not only activate cell cycle progression, but regulate the opportunistic uptake and utilization of nutrients, effectively enabling tumors to maximize growth and drug resistance in changing tissue and systemic microenvironments. Shifts in chromatin architecture are central to this dynamic behavior. Further, changes in nutrient uptake and utilization directly affect chromatin structure. In this review, we describe a set of recent discoveries of metabolic and epigenetic reprogramming in cancer, and especially focus on the genomically well-characterized brain tumor, glioblastoma. Further, we discuss a new mode of metabolic regulation driven by epigenetic mechanisms, that enables cancer cells to autonomously activate iron metabolism for their survival. Together, these underscore the integration of genetic mutations with metabolic reprogramming and epigenetic shifts in cancer, suggesting a new means to identifying patient subsets suitable for specific precision therapeutics.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"53 1","pages":"1-10"},"PeriodicalIF":2.4,"publicationDate":"2020-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37762132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Incremental Growth Lines in Mouse Molar Dentin Represent 8-hr Ultradian Rhythm.","authors":"Ryutaro Ono, Nobuya Koike, Hitoshi Inokawa, Yoshiki Tsuchiya, Yasuhiro Umemura, Toshiro Yamamoto, Narisato Kanamura, Kazuhiro Yagita","doi":"10.1267/ahc.19017","DOIUrl":"https://doi.org/10.1267/ahc.19017","url":null,"abstract":"<p><p>Rhythmic incremental growth lines occur in dental hard tissues of vertebrates, and dentinogenesis in rodent incisors is suggested to be controlled by the 24-hr circadian clock. Rodent incisors continue to grow throughout the animal's life; however, similar to human teeth, rodent molars stop growing after crown formation. This similarity suggests that the mouse molar is an excellent model to understand the molecular mechanisms underlying growth of human teeth. However, not much is known about the rhythmic dentinogenesis in mouse molars. Here, we investigated the incremental growth lines in mouse molar dentin using tetracycline as the growth marker. The incremental growth lines were observed to be generated at approximately 8-hr intervals in wild-type mice housed under 12:12 hr light-dark conditions. Moreover, the 8-hr rhythmic increments persisted in the wild-type and <i>Bmal1<sup>-/-</sup></i> mice housed in constant darkness, where <i>Bmal1<sup>-/-</sup></i> mice become behaviorally arrhythmic. These results revealed that the dentinogenesis in mouse molars underlie the ultradian rhythms with around 8-hr periodicity. Further, the circadian clock does not seem to be involved in this process, providing new insight into the mechanisms involved in the tooth growth.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 6","pages":"93-99"},"PeriodicalIF":2.4,"publicationDate":"2019-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37594548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Localization and Accumulation Studies of Dacomitinib in Rat Intestines and Skin by Immunohistochemistry.","authors":"Yutaro Yamamoto, Tetsuya Saita, Asuki Oka, Hiroto Kataoka, Masashi Shin","doi":"10.1267/ahc.19031","DOIUrl":"https://doi.org/10.1267/ahc.19031","url":null,"abstract":"<p><p>Dacomitinib, a second-generation tyrosine kinase inhibitor, was irreversible inhibitor forming covalent bonds with the kinase domains of EGFR and other ErbB family receptors. Dacomitinib has been approved for the treatment of locally advanced or metastatic non-small cell lung cancer. In this study, we aimed to develop an immunohistochemistry to detect dacomitinib-ErbB family receptor conjugates. Immunostaining was performed in rat intestine and skin tissues after oral administration of dacomitinib. Following a single oral dose of dacomitinib, strong staining was observed after 24 hr in the ileum and colon, with only slight staining in the duodenum and jejunum. In the skin, strong staining was observed in the epidermis, hair follicles, and sebaceous glands. Moreover, significant amounts of dacomitinib remained for up to 72 hr post-administration in the ileum, colon, and skin. This report is the first to elucidate the localization and accumulation of dacomitinib in the rat intestine and skin and should be valuable during efforts to clarify the mechanism dacomitinib-induced diarrhea or skin toxicities.</p>","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 6","pages":"101-106"},"PeriodicalIF":2.4,"publicationDate":"2019-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37594549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hypothalamic Kisspeptin Expression in Hyperandrogenic Female Rats and Aging Rats","authors":"K. Iwata, Yuyu Kunimura, H. Ozawa","doi":"10.1267/ahc.19013","DOIUrl":"https://doi.org/10.1267/ahc.19013","url":null,"abstract":"Hypothalamic kisspeptin neurons stimulate gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) release. Kisspeptin neurons in the anteroventral periventricular nucleus (AVPV) of rats induce an LH surge for ovulation, and those in the arcuate nucleus (ARC) regulate pulsatile LH secretion for follicle development and spermatogenesis. Dysfunction of kisspeptin neurons thus reduces the reproductive function. This review focuses on the effect of androgen or aging on kisspeptin expression in rats. Although androgen directly suppresses ARC kisspeptin neurons in female rats, the AVPV kisspeptin neurons are hardly affected. In rats, plasma LH concentrations decrease in both sexes with aging, and ARC kisspeptin expression also decreases in old rats compared with young rats. In addition, kisspeptin neurons may be associated with hyperprolactinemia in old female rats because they are known to release prolactin through hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons. Hypothalamic kisspeptin neurons are thus the main regulator to secrete LH, and inhibition of kisspeptin expression leads to various kinds of reproductive dysfunction.","PeriodicalId":6888,"journal":{"name":"Acta Histochemica Et Cytochemica","volume":"52 1","pages":"85 - 91"},"PeriodicalIF":2.4,"publicationDate":"2019-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1267/ahc.19013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42066040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}