PubMed · 15603448
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Gregor Rothe, Mariam Klouche. 2004. Phagocyte function.. https://doi.org/10.1016/s0091-679x(04)75029-3
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The recent discovery of mitochondrial nitric-oxide synthase (mtNOS) has provided novel information on mitochondrial biology. mtNOS, localized at the inner membrane, functions as one of the important regulatory factors that affect cellular respiration in mitochondria. The distribution of mtNOS in diverse organs of many species suggests its biological importance. Changes in mtNOS expression and activity in many pathophysiological situations may imply its significant involvement in various NO-related biological phenomena. The functional coordination of mtNOS with other NOSs present in the same or adjacent tissues is unknown as it is most of the regulatory mechanisms of mtNOS expression. Thus, future studies will be required to validate the physiological significance of mtNOS, and to elucidate its regulatory mechanisms on cellular energy metabolism in mitochondria.
1Alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)) stimulates the activity of steroid sulphatase (STS) in myeloid cells [Hughes et al., 2001, 2005]. This was attenuated by inhibitors of phospholipase D (PLD) (n-butanol, 2,3-diphosphoglyceric acid, C(2)-ceramide) and phosphatidate phosphohydrolase (PAP) (propranolol and chlorpromazine), but was unaffected by inhibitors of phospholipase C. The 1alpha,25(OH)(2)D(3)-induced STS activity was also attenuated by inhibitors of protein kinase Calpha and protein kinase Cdelta (Go 6976, HBDDE and rottlerin), but not by an inhibitor of protein kinase Cbeta (LY379196). Additionally, 1alpha,25(OH)(2)D(3)-induced STS activity was attenuated by inhibitors of RAS (manumycin A), RAF (GW5074), MEK (PD098059 and U1026) and JNK (SP600125), but not p38 (PD169316). 1alpha,25(OH)(2)D(3) produced a rapid and long lasting stimulation of the ERK-MAP kinase signalling cascade in HL60 myeloid leukaemic cells. This 'non-genomic' effect of 1alpha,25(OH)(2)D(3) blocked by pharmacological antagonists of nuclear vitamin D receptors (VDR(nuc)) and does not appear to require hetero-dimerisation with the retinoid-X receptor (RXR). Inhibitors of the Src tyrosine kinase (PP1), RAS (manumycin A), RAS-RAF interactions (sulindac sulphide and RAS inhibitory peptide), RAF (GW5074 or chloroquine), and protein kinase Calpha (HBDDE) abrogated the 1alpha,25(OH)(2)D(3)-stimulated increase in ERK-MAP kinase activity. Taken together, these results show that 1alpha,25(OH)(2)D(3)/VDR(nuc) activation of the RAS/RAF/ERK-MAP kinase signalling pathway plays an important role in augmenting STS activity in human myeloid leukaemic cell lines.
Many plants acquire a significant proportion of their nutrient requirements through mutualistic symbiotic interactions with micro-organisms. Legumes in particular acquire the macronutrients nitrogen and phosphorus, and most likely an array of micro-nutrients, from interactions with nitrogen-fixing bacteria and with mycorrhizal fungi. Although the structures formed to support these interactions are different (nodules compared with arbuscules), there is conservation in early signalling between these two symbioses. It is likely that different receptors for rhizobial or mycorrhizal signals induce responses that feed into a common signalling pathway. In the nodulation signalling pathway, calcium plays an essential role as a secondary messenger, and the component that probably transduces the calcium signal is a unique calcium-activated kinase that is required for both mycorrhization and nodulation. The nodulation signalling pathway contains transcriptional regulators downstream of the calcium-activated kinase that are not required for the mycorrhizal symbiosis. This suggests that different symbiosis-specific signalling pathways are activated downstream of the calcium-activated kinase, and raises the question of how specificity of gene induction can be achieved in two pathways that are both likely to use calcium and a unique calcium-activated kinase to induce different downstream events.