Astronauts experience osteoporosis‐like loss of bone mass because of microgravity conditions during space flight. To prevent bone loss, they need a riskless and antiresorptive drug. Melatonin is reported to suppress osteoclast function. However, no studies have examined the effects of melatonin on bone metabolism under microgravity conditions. We used goldfish scales as a bone model of coexisting osteoclasts and osteoblasts and demonstrated that mRNA expression level of acetylserotonin O‐methyltransferase, an enzyme essential for melatonin synthesis, decreased significantly under microgravity. During space flight, microgravity stimulated osteoclastic activity and significantly increased gene expression for osteoclast differentiation and activation. Melatonin treatment significantly stimulated Calcitonin (an osteoclast‐inhibiting hormone) mRNA expression and decreased the mRNA expression of receptor activator of nuclear factor κB ligand (a promoter of osteoclastogenesis), which coincided with suppressed gene expression levels for osteoclast functions. This is the first study to report the inhibitory effect of melatonin on osteoclastic activation by microgravity. We also observed a novel action pathway of melatonin on osteoclasts via an increase in CALCITONIN secretion. Melatonin could be the source of a potential novel drug to prevent bone loss during space flight.
Our pervious electron microscopic studies indicated that Merkel cells (MCs) in the gerbil palatine mucosa were polymorphic, possibly reflecting different function. In order to verify and extend this evidence, the shape of and the innervation to MCs in the palatine mucosa of six different species of rodents including the Mongolian gerbil and the rat were examined by immunohistochemistry and transmission electron microscopy. Immunohistochemistry using anti-cytokeratin 20 (CK20) antibody revealed that in the gerbil palatine mucosa, approximately half of MCs were dendritic. Confocal laser scanning microscopy after double labeling with anti-cytokeratin and anti-PGP 9.5 or anti-Na+/K(+)-ATPase beta 1 subunit antibodies indicated that most of the dendritic MCs (DMCs) in these mucosae were free of innervation. Electron microscopy showed that all species of rodents examined contained abundant dendritic MCs as well as roundish (oval to round) MCs (RMCs) with typical innervation. Secretory granules of the RMCs were usually concentrated at the synaptic site, whereas those of the DMCs tended to accumulate in the tips of the cytoplasmic processes and in the cytoplasm facing the basal lamina. Some MCs showed features intermediate between those of the RMC and DMC. These results indicate that MCs in rodent palatine mucosae are consistently polymorphic, and that DMCs may represent a distinctive subset with specific, presumably including endocrine and paracrine, functions different from those of RMCs.
COX-2 mRNA expression in gastric carcinoma tissue is correlated closely with depth of invasion, indicating that COX-2 is involved in the growth of gastric carcinoma.
Long-chain polyunsaturated fatty acids (LCPUFAs), such as docosahexaenoic acid (DHA, 22:6) and docosapentaenoic acid (DPA, 22:5), have versatile physiologic functions. Studies have suggested that DHA and DPA are beneficial for maintaining sperm quality. However, their mechanisms of action are still unclear because of the poor understanding of DHA/DPA metabolism in the testis. DHA and DPA are mainly stored as LCPUFA-containing phospholipids and support normal spermatogenesis. Long-chain acyl-conenzyme A (CoA) synthetase (ACSL) 6 is an enzyme that preferentially converts LCPUFA into LCPUFA-CoA. Here, we report that ACSL6 knockout (KO) mice display severe male infertility due to attenuated sperm numbers and function. ACSL6 is highly expressed in differentiating spermatids, and ACSL6 KO mice have reduced LCPUFA-containing phospholipids in their spermatids. Delayed sperm release and apoptosis of differentiated spermatids were observed in these mice. The results of this study indicate that ACSL6 contributes to the local accumulation of DHA- and DPA-containing phospholipids in spermatids to support normal spermatogenesis.—Shishikura, K., Kuroha, S., Matsueda, S., Iseki, H., Matsui, T., Inoue, A., Arita, M. Acyl-CoA synthetase 6 regulates long-chain polyunsaturated fatty acid composition of membrane phospholipids in spermatids and supports normal spermatogenic processes in mice.
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