bims-polyam 2021-05-23 papers

Issue of 2021–05–23
five papers selected by
Sebastian J. Hofer, University of Graz

J Pharm Biomed Anal. 2021 May 07. pii: S0731-7085(21)00240-5. [Epub ahead of print]201 114129

Curcumin reverses doxorubicin resistance in colon cancer cells at the metabolic level.

Nan Zhang, Ming Gao, Zihan Wang, Jingxian Zhang, Weiqi Cui, Jinjin Li, Xiaolin Zhu, Hang Zhang, Dong-Hua Yang, Xia Xu.

Doxorubicin (Dox) is commonly used for the treatment of malignant tumors, including colon cancer. However, the development of P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in tumor chemotherapy has seriously reduced the therapeutic efficacy of Dox. Natural product curcumin (Cur) was demonstrated to have a variety of pharmacological effects, such as anti-tumor, anti-oxidation and anti-aging activities. Here, we examined the MDR reversal capability of Cur in drug sensitive-(SW620) and resistant-(SW620/Ad300) colon cancer cells, and elucidated the underlying molecular mechanisms at the metabolic level. It was found that Cur reversed P-gp-mediated resistance in SW620/Ad300 cells by enhancing the Dox-induced cytotoxicity and apoptosis. Further mechanistic studies indicated that Cur inhibited the ATP-dependent transport activity of P-gp, thereby increasing the intra-celluar accumulation of Dox in drug-resistant cells. Metabolomics analysis based on UPLC-MS/MS showed that the MDR phenomenon in SW620/Ad300 cells was closely correlated with the upregulation of spermine and spermidine synthesis and D-glutamine metabolism. Cur significantly inhibited the biosynthesis of spermine and spermidine by decreasing the expression of ornithine decarboxylase (ODC) and suppressed D-glutamine metabolism, which in turn decreased the anti-oxidative stress ability and P-gp transport activity of SW620/Ad300 cells, eventually reversed MDR. These findings indicated the MDR reversal activity and the related mechanism of action of Cur, suggesting that Cur could be a promising MDR reversal agent for cancer treatment.

Keywords: Biosynthesis of polyamines; Colon cancer; Curcumin; D-glutamine metabolism; Metabolomics; P-glycoprotein

DOI: https://doi.org/10.1016/j.jpba.2021.114129

Physiol Rep. 2021 May;9(9): e14864

TRPC1-mediated Ca2+ signaling enhances intestinal epithelial restitution by increasing α4 association with PP2Ac after wounding.

Navneeta Rathor, Hee Kyoung Chung, Jia-Le Song, Shelley R Wang, Jian-Ying Wang, Jaladanki N Rao.

Gut epithelial restitution after superficial wounding is an important repair modality regulated by numerous factors including Ca2+ signaling and cellular polyamines. Transient receptor potential canonical-1 (TRPC1) functions as a store-operated Ca2+ channel in intestinal epithelial cells (IECs) and its activation increases epithelial restitution by inducing Ca2+ influx after acute injury. α4 is a multiple functional protein and implicated in many aspects of cell functions by modulating protein phosphatase 2A (PP2A) stability and activity. Here we show that the clonal populations of IECs stably expressing TRPC1 (IEC-TRPC1) exhibited increased levels of α4 and PP2A catalytic subunit (PP2Ac) and that TRPC1 promoted intestinal epithelial restitution by increasing α4/PP2Ac association. The levels of α4 and PP2Ac proteins increased significantly in stable IEC-TRPC1 cells and this induction in α4/PP2Ac complexes was accompanied by an increase in IEC migration after wounding. α4 silencing by transfection with siRNA targeting α4 (siα4) or PP2Ac silencing destabilized α4/PP2Ac complexes in stable IEC-TRPC1 cells and repressed cell migration over the wounded area. Increasing the levels of cellular polyamines by stable transfection with the Odc gene stimulated α4 and PP2Ac expression and enhanced their association, thus also promoting epithelial restitution after wounding. In contrast, depletion of cellular polyamines by treatment with α-difluoromethylornithine reduced α4/PP2Ac complexes and repressed cell migration. Ectopic overexpression of α4 partially rescued rapid epithelial repair in polyamine-deficient cells. These results indicate that activation of TRPC1-mediated Ca2+ signaling enhances cell migration primarily by increasing α4/PP2Ac associations after wounding and this pathway is tightly regulated by cellular polyamines.

Keywords: IEC-6 cells; TRPC1; cell migration; epithelial restitution; mucosal injury; ornithine decarboxylase; polyamines

DOI: https://doi.org/10.14814/phy2.14864

Plant Cell Rep. 2021 May 18.

Exogenous melatonin regulates endogenous phytohormone homeostasis and thiol-mediated detoxification in two indica rice cultivars under arsenic stress.

Santanu Samanta, Aditya Banerjee, Aryadeep Roychoudhury.

KEY MESSAGE: Melatonin enhanced arsenic (As) tolerance by inhibiting As bioaccumulation, modulating the expression of As transporters and phytohormone homeostasis, leading to efficient utilization of thiol machinery for sequestration and detoxification of this toxic metalloid. The present study was aimed at investigating the influence of exogenous melatonin on the regulation of endogenous plant growth regulators and their cumulative effects on metal(loid)-binding ligands in two contrasting indica rice cultivars, viz., Khitish (arsenic sensitive) and Muktashri (arsenic tolerant) under arsenic stress. Melatonin supplementation ameliorated arsenic-induced perturbations by triggering endogenous levels of gibberellic acid and melatonin, via up-regulating the expression of key biosynthetic genes like GA3ox, TDC, SNAT and ASMT. The endogenous abscisic acid content was also enhanced upon melatonin treatment by induced expression of the key anabolic gene, NCED3 and concomitant suppression of ABA8ox1. Enhanced melatonin content induced accumulation of higher polyamines (spermidine and spermine), together with up-regulation of SPDS and SPMS in Khitish, thereby modulating stress condition. On the contrary, melatonin escalated putrescine and spermidine levels in Muktashri, via enhanced expression of ADC and SAMDC. The role of melatonin appeared to be more prominent in Khitish, as evident from better utilization of thiol components like cysteine, GSH, non-protein thiols and phytochelatins, with higher GSH/GSSG ratio, despite down-regulated expression of corresponding thiol-metabolic genes (OsMT2 and OsPCS1) to deal with arsenic toxicity. The extent of arsenic bioaccumulation, which was magnified several folds, particularly in Khitish, was decreased upon melatonin application. Overall, our observation highlighted the fact that melatonin enhanced arsenic tolerance by inhibiting arsenic bioaccumulation, via modulating the expression levels of selected arsenic transporters (OsNramp1, OsPT2, OsPT8, OsLsi1) and controlling endogenous phytohormone homeostasis, leading to efficient utilization of thiol machinery for sequestration and detoxification of this toxic metalloid.

Keywords: Arsenate; Arsenic transporter; Glutathione; Melatonin; Phytochelatin; Phytohormones; Rice

DOI: https://doi.org/10.1007/s00299-021-02711-7

Sci Rep. 2021 May 21. 11(1): 10669

Spermine mediated improvements on stomatal features, growth, grain filling and yield of rice under differing water availability.

Zulkarami Berahim, Deivaseeno Dorairaj, Mohamad Husni Omar, Halimi Mohd Saud, Mohd Razi Ismail.

Rice which belongs to the grass family is vulnerable to water stress. As water resources get limited, the productivity of rice is affected especially in granaries located at drought prone areas. It would be even worse in granaries located in drought prone areas such as KADA that receives the lowest rainfall in Malaysia. Spermine (SPM), a polyamine compound that is found ubiquitiosly in plants is involved in adaptation of biotic and abiotic stresses. The effect of SPM on growth,grain filling and yield of rice at three main granaries namely, IADA BLS, MADA and KADA representing unlimited water, limited water and water stress conditions respectively, were tested during the main season. Additinally, the growth enhancer was also tested during off season at KADA. Spermine increased plant height, number of tillers per hill and chlorophyll content in all three granaries. Application of SPM improved yield by 38, 29 and 20% in MADA, KADA and IADA BLS, respectively. Harvest index showed 2.6, 6 and 16% increases at IADA BLS, KADA and MADA, respectively in SPM treated plants as compared to untreated. Except for KADA which showed a reduction in yield at 2.54 tha-1, SPM improved yield at MADA, 7.21 tha-1 and IADA BLS, 9.13 tha-1 as compared to the average yield at these respective granaries. In the second trial, SPM increased the yield to 7.0 and 6.4 tha-1 during main and off seasons, respectively, indicating that it was significantly higher than control and the average yield reported by KADA. The yield of SPM treatments improved by 25 and 33% with an increment of farmer's income at main and off seasons, respectively. Stomatal width was significantly higher than control at 11.89 µm. In conclusion, irrespective of the tested granaries and rice variety, spermine mediated plots displayed increment in grain yield.

DOI: https://doi.org/10.1038/s41598-021-89812-1

Plant Physiol Biochem. 2021 May 08. pii: S0981-9428(21)00215-1. [Epub ahead of print]164 237-246

RBOH1-dependent H2O2 mediates spermine-induced antioxidant enzyme system to enhance tomato seedling tolerance to salinity-alkalinity stress.

Jiwen Xu, Zhen Kang, Keyu Zhu, Dingkang Zhao, Yajing Yuan, Shichun Yang, Wentian Zhen, Xiaohui Hu.

Salinity-alkalinity stress is a limiting factor in tomato production in the world. Plants perceive salinity-alkalinity stress by activating signaling pathways to increase plant tolerance (Xu et al., 2020). Here, we investigated whether spermine (Spm) induces respiratory burst oxidase homolog 1 (RBOH1) and hydrogen peroxide (H2O2) signaling in response to salinity-alkalinity stress in tomato. The results showed that exogenous Spm induced the expression of RBOH1 and the accumulation of H2O2 under normal condition. Accordingly, we tested the function of H2O2 signal in tomato seedlings and found that exogenous H2O2 increased the expression levels of Cu/Zn-superoxide dismutase (Cu/Zn-SOD), catalase 1 (CAT1), cytosolic ascorbate peroxidase (cAPX), and glutathione reductase 1 (GR1) and the activities of SOD (EC 1.15.1.1), CAT (EC 1.11.1.6), ascorbate peroxidase (APX; EC 1.11.1.11), and GR (EC 1.6.4.2) in tomato seedlings under salinity-alkalinity stress. DMTU increased the malondialdehyde (MDA) content and relative electrical conductivity, and the relative water content (RWC), and accelerated leaf yellowing in tomato seedlings under salinity-alkalinity stress, even though we sprayed Spm on tomato leaves. We also found that RBOH1 silencing decreased the expression levels of Cu/Zn-SOD, CAT1, cAPX, and GR1 and the activities of SOD, CAT, APX, and GR when tomato seedlings were under salinity-alkalinity stress. Exogenous Spm did not increase RWC and decrease MDA content in RBOH1 silencing tomato seedlings under salinity-alkalinity stress.

Keywords: H(2)O(2); Redox homeostasis; Salinity–alkalinity stress; Spermine; Tomato seedling

DOI: https://doi.org/10.1016/j.plaphy.2021.04.017