The nitrification inhibitor 1,9-decanediol from rice roots promotes root growth in Arabidopsis through involvement of ABA and PIN2-mediated auxin signaling.

1,9-decanediol (1,9-D) is a biological nitrification inhibitor secreted in roots, which effectively inhibits soil nitrifier activity and reduces nitrogen loss from agricultural fields. However, the effects of 1,9-D on plant root growth and the involvement of signaling pathways in the plant response to 1,9-D have not been investigated. Here, we report that 1,9-D, in the 100-400 µM concentration range, promotes primary root length in Arabidopsis seedlings at 3d and 5d, by 10.1%-33.3% and 6.9%-32.6%, and, in a range of 50-200 µM, leads to an increase in the number of lateral roots. 150 µM 1,9-D was found optimum for the positive regulation of root growth. qRT-PCR analysis reveals that 1,9-D can significantly increase AtABA3 gene expression and that a mutation in ABA3 results in insensitivity of root growth to 1,9-D. Moreover, through pharmacological experiments, we show that exogenous addition of ABA (abscisic acid) with 1,9-D enhances primary root length by 23.5%-63.3%, and an exogenous supply of 1,9-D with the ABA inhibitor Flu reduces primary root length by 1.0%-14.3%. Primary root length of the pin2/eir1-1 is shown to be insensitive to both exogenous addition of 1,9-D and ABA, indicating that the auxin carrier PIN2/EIR1 is involved in promotion of root growth by 1,9-D. These results suggest a novel for 1,9-D in regulating plant root growth through ABA and auxin signaling.

Mir223 restrains autophagy and promotes CNS inflammation by targeting ATG16L1.

Microglia are innate immune cells in the central nervous system (CNS), that supplies neurons with key factors for executing autophagosomal/lysosomal functions. Macroautophagy/autophagy is a cellular catabolic process that maintains cell balance in response to stress-related stimulation. Abnormal autophagy occurs with many pathologies, such as cancer, and autoimmune and neurodegenerative diseases. Hence, clarification of the mechanisms of autophagy regulation is of utmost importance. Recently, researchers presented microRNAs (miRNAs) as novel and potent modulators of autophagic activity. Here, we found that Mir223 deficiency significantly ameliorated CNS inflammation, demyelination and the clinical symptoms of experimental autoimmune encephalomyelitis (EAE) and increased resting microglia and autophagy in brain microglial cells. In contrast, the autophagy inhibitor 3-methylademine (3-MA) aggravated the clinical symptoms of EAE in wild-type (WT) and Mir223-deficienct mice. Furthermore, it was confirmed that Mir223 deficiency in mice increased the protein expression of ATG16L1 (autophagy related 16-like 1 [S. cerevisiae]) and LC3-II in bone marrow-derived macrophage cells compared with cells from WT mice. Indeed, the cellular level of Atg16l1 was decreased in BV2 cells upon Mir223 overexpression and increased following the introduction of antagomirs. We also showed that the 3' UTR of Atg16l1 contained functional Mir223-responsive sequences and that overexpression of ATG16L1 returned autophagy to normal levels even in the presence of Mir223 mimics. Collectively, these data indicate that Mir223 is a novel and important regulator of autophagy and that Atg16l1 is a Mir223 target in this process, which may have implications for improving our understanding of the neuroinflammatory process of EAE. Abbreviations: 3-MA: 3-methylademine; ACTB/ß-actin: actin, beta; ATG: autophagy related; ATG16L1: autophagy related 16-like 1 (S. cerevisiae); BECN1: beclin 1, autophagy related; CNR2: cannabinoid receptor 2 (macrophage); CNS: central nervous system; CQ: chloroquine; EAE: experimental autoimmune encephalomyelitis; FOXO3: forkhead box O3; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; H&E: hematoxylin and eosin; ITGAM: integrin alpha M; LPS: lipoplysaccharide; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; miRNAs: microRNAs; MS: multiple sclerosis; PPARG: peroxisome proliferator activated receptor gamma; PTPRC: protein tyrosine phosphatase, receptor type, C; RA: rheumatoid arthritis; SQSTM1: sequestosome 1; TB: tuberculosis; TIMM23: translocase of inner mitochondrial membrane 23; TLR: toll-like receptor.

Adiponectin modulates oxidative stress-induced mitophagy and protects C2C12 myoblasts against apoptosis.

Adiponectin (APN), also known as apM1, Acrp30, GBP28 and adipoQ, is a circulating hormone that is predominantly produced by adipose tissue. Many pharmacological studies have demonstrated that this protein possesses potent anti-diabetic, anti-atherogenic and anti-inflammatory properties. Although several studies have demonstrated the antioxidative activity of this protein, the regulatory mechanisms have not yet been defined in skeletal muscles. The aim of the present study was to examine the cytoprotective effects of APN against damage induced by oxidative stress in mouse-derived C2C12 myoblasts. APN attenuated H2O2-induced growth inhibition and exhibited scavenging activity against intracellular reactive oxygen species that were induced by H2O2. Furthermore, treating C2C12 cells with APN significantly induced heme oxygenase-1 (HO-1) and nuclear factor-erythroid 2 related factor 2 (Nrf2). APN also suppressed H2O2-induced mitophagy and partially inhibited the colocalization of mitochondria with autophagosomes/lysosomes, correlating with the expression of Pink1 and Parkin and mtDNA. Moreover, APN protected C2C12 myoblasts against oxidative stress-induced apoptosis. Furthermore, APN significantly reduced the mRNA and protein expression levels of Bax. These data suggest that APN has a moderate regulatory role in oxidative stress-induced mitophagy and suppresses apoptosis. These findings demonstrate the antioxidant potential of APN in oxidative stress-associated skeletal muscle diseases.