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• KAR 1 improved the production of Ca2+–CaM, BL, JA and SAB in S. miltiorrhiza hairy roots. • Ca2+ and BL seem to have a parallel relationship and acts as upstream signaling molecule to medicate the production of JA. • Ca2+–CaM, BL mediated the KAR 1 -induced increase of SAB dependent on the generation of JA in S. miltiorrhiza hairy roots. The effects of smoke-derived karrikins (KAR 1) on the contents of endogenous signal molecules including (Ca2+)–calmodulin (CaM), brassinolide (BL) and Jasmonic acid (JA) and secondary metabolite Salvianolic acid B (SAB) in Salvia miltiorrhiza hairy roots have been investigated. The results showed that the burst of Ca2+–CaM, BL and JA were early responses of S. miltiorrhiza responding to KAR 1. Treatments with exogenous CaCl 2 and BL dramatically improved the level of JA, while JA inhibitor salicylhydroxamic acid/n-propylgallate (SHAM/PrGall) did not influence levels of Ca2+ and BL in S. miltiorrhiza hairy roots. Furthermore, pretreatments with the Ca2+ channel blockers LaCl 3 (La3+) and Verapamil (VERA), and CaM antagonists [N-(6-amin-ohexyl)-5-chloro-1-naphthalene sulfonamide hydrochloride] (W 7) and trifluoperazine (TFP) substantially reduced KAR 1 -induced BL accumulation, while the Ca2+ production induced by KAR 1 was reduced by BL inhibitor Brassinazole (BRz). It suggested that Ca2+ and BL seem to have a parallel relationship and act as upstream signaling molecules to medicate the production of JA. The inhibitory effects of VERA, W 7 , BRz and SHAM toward SAB production induced by the KAR 1 could be reversed by exogenous jasmonate methyl (JAMe), while the exogenous CaCl 2 and BL had no similar effects. It proved that Ca2+–CaM, BL mediated the KAR 1 -induced increase of SAB dependent on the generation of JA in S. miltiorrhiza hairy roots. This study help us understand the regulatory mechanism of Ca2+–CaM, BL, JA on KAR 1 -induced accumulation of SAB in S. miltiorrhiza hairy roots. [ABSTRACT FROM AUTHOR]

The dwarf musk deer, or Chinese forest musk deer (Moschus berezovskii) is an endangered artiodactyl species native to a narrow region in southern and central China as well as northernmost Vietnam. This species is well known for the habit of male musk deer to secrete musk from the musk gland. Unmated male forest musk deer secrete a greater amount of musk than mated males, which probably allows them to attract a greater number of females. However, transcriptome data for this species are deficient, and the potential transcriptional pathways of musk production remain unknown. In this study, we used RNA-sequencing (RNA-Seq) to perform an in-depth survey of transcriptome data from musk gland and to compare the transcriptome differences between mated- and unmated sexually mature Chinese forest musk deer. There were 13,009 and 12,995 genes were expressed in unmated and mated musk glands tissue. In addition to analyzing these genes, we analyzed the differentially expressed genes in musk gland tissue between mated and unmated Chinese forest musk deer males. One hundred and thirty seven genes were found differentially expressed. We found that some genes in "PPAR signaling pathway", "PI3K-Akt signaling pathway" and "Thyroid hormone synthesis" pathways may be associated with musk production and the secretion of the musk deer. The annotated genes and differentially expressed genes in this study can be applied in conservation or utilization study of musk deer in the future. [ABSTRACT FROM AUTHOR]

Avicins, a family of plant triterpene electrophiles, can trigger apoptosis-associated tumor cell death, and suppress chemical-induced carcinogenesis by its anti-inflammatory, anti-mutagenic, and antioxidant properties. Here, we show that tumor cells treated with benzyloxycarbonylvalyl-alanyl–aspartic acid (O-methyl)–fluoro-methylketone, an apoptosis inhibitor, and Bax−/−Bak−/− apoptosis-resistant cells can still undergo cell death in response to avicin D treatment. We demonstrate that this non-apoptotic cell death is mediated by autophagy, which can be suppressed by chloroquine, an autophagy inhibitor, and by specific knockdown of autophagy-related gene-5 (Atg5) and Atg7. Avicin D decreases cellular ATP levels, stimulates the activation of AMP-activated protein kinase (AMPK), and inhibits mammalian target of rapamycin (mTOR) and S6 kinase activity. Suppression of AMPK by compound C and dominant-negative AMPK decreases avicin D-induced autophagic cell death. Furthermore, avicin D-induced autophagic cell death can be abrogated by knockdown of tuberous sclerosis complex 2 (TSC2), a key mediator linking AMPK to mTOR inhibition, suggesting that AMPK activation is a crucial event targeted by avicin D. These findings indicate the therapeutic potential of avicins by triggering autophagic cell death.Cell Death and Differentiation (2007) 14, 1948–1957; doi:10.1038/sj.cdd.4402207; published online 10 August 2007 [ABSTRACT FROM AUTHOR]

Although smoke-water (SW) and butenolide (KAR 1) isolated from smoke show stimulating effects on the production of secondary metabolites in medicinal plants, the underlying mechanisms are not well understood. This study was initiated to investigate the signal molecule in the KAR 1 -induced tanshinones biosynthesis in Salvia miltiorrhiza hairy root. KAR 1 treatment resulted in substantial improvement in the accumulation of jasmonic acid (JA), followed by an increase in lipophilic tanshinones production in S. miltiorrhiza hairy root. Treatment of external JA stimulated the biosynthesis of tanshinones without KAR 1 treatment. KAR 1 -stimulated tanshinones biosynthesis was inhibited with the treatment of SHAM and PrGall, which are JA synthesis inhibitors. This study indicated that JA serves as a role in the signal transduction involved in KAR 1 -stimulated tanshinones biosynthesis in the S. miltiorrhiza. • JA serves as a role in the signal transduction involved in KAR 1 -stimulated tanshinones biosynthesis in the S. miltiorrhiza. • KAR 1 could induce the germination of JA and accumulation of tanshinones in S. miltiorrhiza. [ABSTRACT FROM AUTHOR]

Liver kinase B1 (LKB1, also known as serine/threonine kinase 11, STK11) is a tumor suppressor mutated in Peutz-Jeghers syndrome and in a variety of sporadic cancers. Herein, we demonstrate that LKB1 controls the levels of intracellular reactive oxygen species (ROS) and protects the genome from oxidative damage. Cells lacking LKB1 exhibit markedly increased intracellular ROS levels, excessive oxidation of DNA, increased mutation rates and accumulation of DNA damage, which are effectively prevented by ectopic expression of LKB1 and by incubation with antioxidant N-acetylcysteine. The role of LKB1 in suppressing ROS is independent of AMP-activated protein kinase, a canonical substrate of LKB1. Instead, under the elevated ROS, LKB1 binds to and maintains the activity of the cdc42-PAK1 (p21-activated kinase 1) complex, which triggers the activation of p38 and its downstream signaling targets, such as ATF-2, thereby enhancing the activity of superoxide dismutase-2 and catalase, two antioxidant enzymes that protect the cells from ROS accumulation, DNA damage and loss of viability. Our results provide a new paradigm for a non-canonical tumor suppressor function of LKB1 and highlight the importance of targeting ROS signaling as a potential therapeutic strategy for cancer cells lacking LKB1. [ABSTRACT FROM AUTHOR]