PMID- 36222367 OWN - NLM STAT- MEDLINE DCOM- 20230217 LR - 20230217 IS - 1471-9053 (Electronic) IS - 0032-0781 (Linking) VI - 64 IP - 1 DP - 2023 Feb 16 TI - Cardenolide Increase in Foxglove after 2,1,3-Benzothiadiazole Treatment Reveals a Potential Link between Cardenolide and Phytosterol Biosynthesis. PG - 107-116 LID - 10.1093/pcp/pcac144 [doi] AB - Cardenolides are steroidal metabolites in Digitalis lanata with potent cardioactive effects on animals. In plants, cardenolides are likely involved in various stress responses. However, the molecular mechanism of cardenolide increase during stresses is mostly unknown. Additionally, cardenolides are proposed to arise from cholesterol, but indirect results show that phytosterols may also be substrates for cardenolide biosynthesis. Here, we show that cardenolides increased after methyl jasmonate (MJ), sorbitol, potassium chloride (KCl) and salicylic acid analog [2,1,3-benzothiadiazole (BTH)] treatments. However, the expression of three known genes for cardenolide biosynthesis did not correlate well with these increases. Specifically, the expression of progesterone-5beta-reductases (P5betaR and P5betaR2) did not correlate with the cardenolide increase. The expression of 3beta-hydroxysteroid dehydrogenase (3betaHSD) correlated with changes in cardenolide levels only during the BTH treatment. Mining the D. lanata transcriptome identified genes involved in cholesterol and phytosterol biosynthesis: C24 sterol sidechain reductase 1 (SSR1), C4 sterol methyl oxidase 1, and 3 (SMO1 and SMO3). Surprisingly, the expression of all three genes correlated well with the cardenolide increase after the BTH treatment. Phylogenetic analysis showed that SSR1 is likely involved in both cholesterol and phytosterol biosynthesis. In addition, SMO1 is likely specific to phytosterol biosynthesis, and SMO3 is specific to cholesterol biosynthesis. These results suggest that stress-induced increase of cardenolides in foxglove may correlate with cholesterol and phytosterol biosynthesis. In summary, this work shows that cardenolides are important for stress responses in D. lanata and reveals a potential link between phytosterol and cardenolide biosynthesis. CI - (c) The Author(s) 2022. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. FAU - Raghavan, Indu AU - Raghavan I AD - Department of Biological Sciences, University at Buffalo, The State University of New York, 109 Cooke Hall, Buffalo, NY 14260, USA. FAU - Ravi Gopal, Baradwaj AU - Ravi Gopal B AD - Department of Biological Sciences, University at Buffalo, The State University of New York, 109 Cooke Hall, Buffalo, NY 14260, USA. FAU - Carroll, Emily AU - Carroll E AD - Department of Biological Sciences, University at Buffalo, The State University of New York, 109 Cooke Hall, Buffalo, NY 14260, USA. FAU - Wang, Zhen Q AU - Wang ZQ AUID- ORCID: 0000-0002-3244-690X AD - Department of Biological Sciences, University at Buffalo, The State University of New York, 109 Cooke Hall, Buffalo, NY 14260, USA. LA - eng GR - 71272/Research Foundation for the State University of New York/ GR - 1919594/National Science Foundation/ PT - Journal Article PL - Japan TA - Plant Cell Physiol JT - Plant & cell physiology JID - 9430925 RN - 0 (Cardenolides) RN - 273-77-8 (benzo-1,2,3-thiadiazole) RN - 0 (Phytosterols) RN - EC 1.- (Oxidoreductases) SB - IM MH - Animals MH - *Digitalis/chemistry/genetics/metabolism MH - Cardenolides/analysis/metabolism MH - *Phytosterols MH - Phylogeny MH - Oxidoreductases/metabolism OTO - NOTNLM OT - Digitalis lanata OT - Cardiac glycosides OT - Methyl jasmonate OT - Salicylic acid OT - Sterol methyl oxidase OT - Sterol sidechain reductase EDAT- 2022/10/13 06:00 MHDA- 2023/02/18 06:00 CRDT- 2022/10/12 07:33 PHST- 2021/10/21 00:00 [received] PHST- 2022/10/04 00:00 [revised] PHST- 2022/10/11 00:00 [accepted] PHST- 2022/10/13 06:00 [pubmed] PHST- 2023/02/18 06:00 [medline] PHST- 2022/10/12 07:33 [entrez] AID - 6759213 [pii] AID - 10.1093/pcp/pcac144 [doi] PST - ppublish SO - Plant Cell Physiol. 2023 Feb 16;64(1):107-116. doi: 10.1093/pcp/pcac144.