Serum metabolomic research of the anti-pulmonary fibrosis effects of Shuangshen Pingfei Formula on bleomycin-induced pulmonary fibrosis rats.

Our previous studies showed that Shuangshen Pingfei Formula (SSPF) exhibited anti-fibrosis effect, but its biochemical changes at the metabolic level remain unclear. In this study, an integrative approach of gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS)-based non-targeted metabolomics and multivariate statistical analysis was employed to explore the metabolic changes of serum samples from different stages of bleomycin-induced pulmonary fibrosis (PF) rats (PFRs: M7, M14, M21 and M28) treated with SSPF extracts. Potential biomarkers for PF were screened. Benzenebutanoic acid, pyroglutamic acid, cholic acid, 1-monopalmitin, succinic acid and palmitoleic acid may be potential biomarkers of the early inflammation stage of PF (M7-M14). 3,4-dimethylbenzoic acid, glutamic acid, glycine, proline, serine, taurine, etc. may be potential biomarkers for the advanced pulmonary fibrosis stage (M21-M28) of PF. The disturbance was mainly related to the disorder of lipid, amino acid metabolism. After SSPF treatment, the disorder was regulated and 67 metabolites were restored to a certain extent. Serine, proline, glutamine, 4-guanidinobutyric acid, phosphatidylethanolamine, lecithin and 9,10-epoxyoctadecene acids may be useful as biomarkers of the anti-fibrosis effect of SSPF.

Arabidopsis CHLOROPHYLLASE 1 protects young leaves from long-term photodamage by facilitating FtsH-mediated D1 degradation in photosystem II repair.

The proteolytic degradation of the photodamaged D1 core subunit during the photosystem II (PSII) repair cycle is well understood, but chlorophyll turnover during D1 degradation remains unclear. Here, we report that Arabidopsis thaliana CHLOROPHYLLASE 1 (CLH1) plays important roles in the PSII repair process. The abundance of CLH1 and CLH2 peaks in young leaves and is induced by high-light exposure. Seedlings of clh1 single and clh1-1/2-2 double mutants display increased photoinhibition after long-term high-light exposure, whereas seedlings overexpressing CLH1 have enhanced light tolerance compared with the wild type. CLH1 is localized in the developing chloroplasts of young leaves and associates with the PSII-dismantling complexes RCC1 and RC47, with a preference for the latter upon exposure to high light. Furthermore, degradation of damaged D1 protein is retarded in young clh1-1/2-2 leaves after 18-h high-light exposure but is rescued by the addition of recombinant CLH1 in vitro. Moreover, overexpression of CLH1 in a variegated mutant (var2-2) that lacks thylakoid protease FtsH2, with which CLH1 interacts, suppresses the variegation and restores D1 degradation. A var2-2 clh1-1/2-2 triple mutant shows more severe variegation and seedling death. Taken together, these results establish CLH1 as a long-sought chlorophyll dephytylation enzyme that is involved in PSII repair and functions in long-term adaptation of young leaves to high-light exposure by facilitating FtsH-mediated D1 degradation.