SUMO2/3 promotes the progression and oxaliplatin resistance of colorectal cancer through facilitating the SUMOylation at Ku80‐K307

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SUMO2/3 promotes the progression and oxaliplatin resistance of colorectal cancer through facilitating the SUMOylation at Ku80-K307

We describes the role for SUMO2/3 during oxaliplatin resistance in CRC and assessed the contribution of Ku80 SUMOylation in this process. Overexpression of SUMO2/3-promoted CRC cell proliferation, invasion, migration in vitro and in vivo. SUMOylation of K307 in Ku80 attenuated the DNA damage of CRC cells caused by oxaliplatin and was consistent with an antiapoptotic role for SUMO2/3.


Abstract

Colorectal cancer (CRC) is one of the most prevalent cancers worldwide and is typically treated with the FOLFOX regimen (folinic acid, 5-fluorouracil, and oxaliplatin). However, oxaliplatin resistance remains a serious clinical problem. In the present study, we found that SUMO2/3 was overexpressed in CRC tissues and exogenous overexpression of SUMO2/3 promoted CRC cell proliferation, extension, and invasion and positively regulated the cell cycle. In contrast, SUMO2/3 gene knockdowns inhibited migration and repressed cell viability in vitro and in vivo. In addition, we found that SUMO2/3 was recruited to the cell nucleus and suppressed oxaliplatin-induced apoptosis of CRC cells. Moreover, Ku80, a DNA-binding protein essential for the repair of DNA double-strand breaks, was confirmed to bind with SUMO2/3. Notably, Ku80 undergoes SUMOylation at K307 by SUMO2/3 and this correlated with apoptosis in CRC cells suffering oxaliplatin stress. Collectively, we found that SUMO2/3 plays a specific role in CRC tumorigenesis and acts through Ku80 SUMOylation which is linked with the development of CRC-oxaliplatin resistance.

Silicon alleviates drought damage by increasing antioxidant and photosynthetic performance in cowpea

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Abstract

Water deficits have been considered the most restrictive environmental constraint on agricultural production worldwide. The current study aimed to investigate the role of silicon nutrition (Si) in activating defence mechanisms against drought damage in cowpea cultivars. The experiments were carried out in a randomized block design in a 2 × 2 × 4 factorial scheme, corresponding to two cowpea cultivars (BRS Novaera and BRS Tumucumaque), two water regimes (control well-irrigated and water deficit) and four Si levels (0, 1.0, 2.0 and 4.0 mM). Plant growth and physiological and biochemical indicators were evaluated 28 days after drought imposition. Drought significantly reduced the photosynthetic pigments (Chl b and Chl total), gas exchanges (net photosynthesis, transpiration and stomatal conductance) and, consequently, all growth parameters of cowpea plants compared with well-irrigated plants. However, Si at 2.0 mM activated critical responses in the BRS Novaera cultivar under drought, almost recovering plant performance and increasing drought tolerance. The beneficial Si-induced effects were closely related to increased accumulation of Si, carbohydrates and free amino acids that likely promoted osmoregulation and were associated with an improved antioxidant system composed of proline and the activity of SOD, CAT and APX. These metabolic alterations were sufficient to enable enhanced net photosynthesis and plant growth. In conclusion, Si counteracts the deleterious effects of water deficit by efficiently inducing antioxidant defence and photosynthetic performance in Novaera plants. Si nutrition may constitute a potential strategy to cultivate cowpea plants in water-scarce areas from arid and semiarid regions.

Adipose tissue‐derived mesenchymal stem cells ameliorate cognitive impairment in Alzheimer’s disease rat model: Emerging role of SIRT1

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Adipose tissue-derived mesenchymal stem cells ameliorate cognitive impairment in Alzheimer's disease rat model: Emerging role of SIRT1

The present study aimed to investigate the therapeutic potential of adipose tissue-derived mesenchymal stem cells (Ad-MSCs) in Alzheimer's disease (AD) rat model, and to explore the possible implication of SIRT1. Our data demonstrated that transplantation of Ad-MSCs alleviated cognitive impairment in AD rats. Additionally, they exhibited anti-amyloidogenic, anti-apoptotic, anti-inflammatory, as well as neurogenic effects. Furthermore, Ad-MSCs were found to mediate their therapeutic effects, at least partially, via modulating both central and systemic SIRT1 levels. Hence, the current study portrays Ad-MSCs as an effective therapeutic approach for AD management and opens the door for future investigations to further elucidate the role of SIRT1 and its interrelated molecular mediators in AD.


Abstract

Alzheimer's disease (AD) is a complex form of neurodegenerative dementia. Growing body of evidence supports the cardinal role of sirtuin1 (SIRT1) in neurodegeneration and AD development. Recently, adipose tissue-derived mesenchymal stem cells (Ad-MSCs) have made their mark for a wide array of regenerative medicine applications, including neurodegenerative disorders. Therefore, the present study aimed to investigate the therapeutic potential of Ad-MSCs in AD rat model, and to explore the possible implication of SIRT1. Ad-MSCs were isolated from rat epididymal fat pads and properly characterized. Aluminum chloride was used to induce AD in rats, and afterward, a group of AD-induced rats received a single dose of Ad-MSCs (2 × 106 cell, I.V per rat). One month after Ad-MSCs transplantation, behavioral tests were done, brain tissues were collected, then histopathological and biochemical assessments were performed. Amyloid beta and SIRT1 levels were determined by enzyme-linked immunosorbent assay. Whereas expression levels of neprilysin, BCL2 associated X protein, B-cell lymphoma-2, interleukin-1β, interleukin-6, and nerve growth factor in hippocampus and frontal cortex brain tissues were assessed using reverse transcriptase quantitative polymerase chain reaction. Our data demonstrated that transplantation of Ad-MSCs alleviated cognitive impairment in AD rats. Additionally, they exhibited anti-amyloidogenic, antiapoptotic, anti-inflammatory, as well as neurogenic effects. Furthermore, Ad-MSCs were found to possibly mediate their therapeutic effects, at least partially, via modulating both central and systemic SIRT1 levels. Hence, the current study portrays Ad-MSCs as an effective therapeutic approach for AD management and opens the door for future investigations to further elucidate the role of SIRT1 and its interrelated molecular mediators in AD.

Salinity effects on the activities of ROS scavenging enzymes in leaves of two sweet potato clones

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Abstract

Sweet potato production, particularly in coastal areas is often prone to salinity. Salt-tolerant clones will be needed to maintain production, but to date, little is known about salt tolerance traits in sweet potato. Salt stress may result in excessive uptake of unwanted ions into plant tissues leading to the formation of reactive oxygen species (ROS), which in turn may destroy membranes and reduce photosynthesis and growth. Antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POX), catalase (CAT), glutathione reductase (GR) and ascorbate peroxidase (APX) scavenge ROS and early changes in the activities of such enzymes could be used to identify salinity tolerant genotypes. Therefore, cuttings of two contrasting cultivars of sweet potato, BARI SP 8 (tolerant) and BARI SP 4 (sensitive) were greenhouse-cultivated in nutrient solution for 21 days and then exposed to 100 mmol NaCl for 7 days. Three, five and seven days after salt application the youngest leaves were sampled individually and enzyme activities, potassium (K) and sodium (Na) concentrations, and SPAD (as a proxy for chlorophyll content) were determined. In both varieties leaf growth was not affected by salinity and young leaves grown under salinity had higher SPAD values than older leaves. Na concentration increased over time, particularly in earlier and in older leaves, whereas K was reduced in younger leaves. In general, enzyme activities were strongly affected by leaf age and leaf position. SOD and APX showed varietal but no salinity effects, CAT increased under salinity in both varieties, whereas POX was strongly reduced and GR was strongly increased under salinity in BARI SP 8 with no effect in BARI SP 4. Enzyme activities were not correlated to leaf Na, neither in relation to leaf age, nor leaf number or duration of salt stress in both varieties. However, varietal differences were observed regarding leaf K. Activities of SOD were highly positive and of CAT highly negatively correlated with leaf K under salinity in BARI SP 8 but not in BARI SP 4, whereas activities of GR and POX were strongly positively correlated with leaf K in BARI SP 4 under salinity but not in BARI SP 8. We conclude that potassium may have a strong regulating role on leaf stress levels and therefore on the activities of antioxidant enzymes. Varieties may differ in their tolerance strategy and we have shown that salinity does not generally increase levels of ROS-scavenging enzymes in sweet potato leaves under salt stress. Confounding factors such as leaf age and leaf position as well as maintaining high leaf level K concentrations need to be considered when evaluating metabolic traits for salinity tolerance traits.