Acid regulation of NaDC-1 requires a functional endothelin B receptor

Metabolically generated acid is the major physiological stimulus for increasing proximal tubule citrate reabsorption, which leads to a decrease in citrate excretion. The activity of the Na-citrate cotransporter, NaDC-1, is increased in vivo by acid ingestion and in vitro by an acidic pH medium. In opossum kidney cells the acid stimulatory effect and the ability of endothelin-1 (ET-1) to stimulate NaDC-1 activity are both blocked by the endothelin B (ETB) receptor antagonist, BQ788. Acid feeding had no effect on brush border membrane NaDC-1 activity in mice in which ETB receptor expression was knocked out, whereas a stimulatory effect was found in wild-type mice. Using ETA/ETB chimeric and ETB C-terminal tail truncated constructs, ET-1 stimulation of NaDC-1 required a receptor C-terminal tail from either ETA or ETB. The ET-1 effect was greatest when either the ETB transmembrane domain and C-terminal tail were present or the ETB C-terminal tail was linked to the ETA transmembrane domain. This effect was smaller when the ETB transmembrane domain was linked to the ETA C-terminal tail. Thus, the acid-activated pathway mediating stimulation of NaDC-1 activity requires a functional ETB receptor in vivo and in vitro, as does acid stimulation of NHE3 activity. Since increased NaDC-1 and NHE3 activities constitute part of the proximal tubule adaptation to an acid load, these studies indicate that there are similarities in the signaling pathway mediating these responses

Oxidative Stress and Carbonyl Lesions in Ulcerative Colitis and Associated Colorectal Cancer

Oxidative stress has long been known as a pathogenic factor of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), but the effects of secondary carbonyl lesions receive less emphasis. In inflammatory conditions, reactive oxygen species (ROS), such as superoxide anion free radical (O2∙-), hydrogen peroxide (H2O2), and hydroxyl radical (HO∙), are produced at high levels and accumulated to cause oxidative stress (OS). In oxidative status, accumulated ROS can cause protein dysfunction and DNA damage, leading to gene mutations and cell death. Accumulated ROS could also act as chemical messengers to activate signaling pathways, such as NF-κB and p38 MAPK, to affect cell proliferation, differentiation, and apoptosis. More importantly, electrophilic carbonyl compounds produced by lipid peroxidation may function as secondary pathogenic factors, causing further protein and membrane lesions. This may in turn exaggerate oxidative stress, forming a vicious cycle. Electrophilic carbonyls could also cause DNA mutations and breaks, driving malignant progression of UC. The secondary lesions caused by carbonyl compounds may be exceptionally important in the case of host carbonyl defensive system deficit, such as aldo-keto reductase 1B10 deficiency. This review article updates the current understanding of oxidative stress and carbonyl lesions in the development and progression of UC and CAC

Physiological, biochemical and transcriptomic studies reveal the mechanisms promoting tiller bud growth under high temperature conditions in japonica rice

High temperature (HT) negatively impacts the initiation and development of tiller buds in japonica rice, resulting in a substantial decrease in yield. However, the physiological and molecular mechanisms alleviating the inhibition of HT on the growth of tiller buds in japonica rice remain elusive. Hence, this study aimed to dissect the underlying mechanisms of normal tiller buds’ growth under HT in japonica rice through comparative physiological, biochemical and transcriptomics analyses of two contrasting varieties, ‘Changgeng 225’ (‘CG225’, heat-tolerant) and ‘Zhonghua 11’ (‘ZH11’, heat-sensitive). Compared with ‘ZH11’, the tiller number of ‘CG225’ decreased less under HT stress. ‘CG225’ outperformance over ‘ZH11’ was due to higher activities of the antioxidant enzymes (SOD, CAT, POD and APX), as well as higher activities of the key enzymes involved in carbon and nitrogen metabolism (NR, GOGAT, GS, GDH, SS and SPS) in tiller buds. In addition, lower contents of the tiller-inhibiting phytohormone ABA and SLs, and higher contents of the tiller-promoting phytohormone CK in ‘CG225’ also promoted the growth of tiller buds. Most of the significant DEGs between ‘CG225’ and ‘ZH11’ under HT conditions were assigned to chloroplast and photosynthesis. We identified potential candidate genes, including transcription factors (EP2, B3, bHLH, MYB, NAC, and WRKY), phytohormone (auxin efflux carriers and ethylene biosynthesis genes), antioxidant system (peroxidases), and sucrose pathway-related genes. Furthermore, ectopic sucrose application significantly alleviated HT inhibitory effects on tiller bud growth of ‘ZH11’ plants. Our results reveal a synergistic control of heat stress by several metabolic mechanisms in japonica rice during tillering and provide fundamental resources for improving rice HT tolerance and production.