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The reduction and the formation of regulatory disulfide bonds serve as a key signaling element in chloroplasts. Members of the thioredoxin (Trx) superfamily of oxidoreductases play a major role in these processes. We have characterized a small family of plant-specific Trxs in Arabidopsis (Arabidopsis thaliana) that are rich in cysteine and histidine residues and are typified by a variable noncanonical redox active site. We found that the redox midpoint potential of three selected family members is significantly less reducing than that of the classic Trxs. Assays of subcellular localization demonstrated that all proteins are localized to the chloroplast. Selected members showed high activity, contingent on a dithiol electron donor, toward the chloroplast 2-cysteine peroxiredoxin A and poor activity toward the chloroplast NADP-malate dehydrogenase. The expression profile of the family members suggests that they have distinct roles. The intermediate redox midpoint potential value of the atypical Trxs might imply adaptability to function in modulating the redox state of chloroplast proteins with regulatory disulfides.

RB60 is an atypical protein disulfide isomerase (PDI) that functions as a member of a redox regulatory protein complex controlling translation in the chloroplast of Chlamydomonas reinhardtii, but also contains a C-terminal endoplasmic reticulum (ER) retention signal, -KDEL. Here, we show by fluorescence microscopy that RB60 resides in the chloroplast but also outside of the chloroplast colocalized with BiP, an ER marker protein. RB60 accumulates in microsomes that exhibit a typical ER magnesium-shift, and cotranslationally translocates into ER microsomes. The first 50-aa leader of RB60 is sufficient for both chloroplast and ER targeting. The leader is cleaved upon translocation into the ER, whereas it remains intact after import to the chloroplast. The leader sequence also contains an acidic domain that appears necessary for the protein's association with the thylakoid membranes. Based on these and additional results, we propose that the dual localization of RB60 occurs via the two conserved transport mechanisms, to the chloroplast and to the ER, that the chloroplast RB60 most likely carries an additional function in the ER, and that its mode of transport, including the differential cleavage of its N terminus, plays an important role in its suborganellar localization and organellar-specific function.

The reduction and the formation of regulatory disulfide bonds serve as a key signaling element in chloroplasts. Members of the thioredoxin (Trx) superfamily of oxidoreductases play a major role in these processes. We have characterized a small family of plant-specific Trxs in Arabidopsis (Arabidopsis thaliana) that are rich in cysteine and histidine residues and are typified by a variable noncanonical redox active site. We found that the redox midpoint potential of three selected family members is significantly less reducing than that of the classic Trxs. Assays of subcellular localization demonstrated that all proteins are localized to the chloroplast. Selected members showed high activity, contingent on a dithiol electron donor, toward the chloroplast 2-cysteine peroxiredoxin A and poor activity toward the chloroplast NADP-malate dehydrogenase. The expression profile of the family members suggests that they have distinct roles. The intermediate redox midpoint potential value of the atypical Trxs might imply adaptability to function in modulating the redox state of chloroplast proteins with regulatory disulfides.

Approximately one in five patients undergoing coronary artery bypass graft (CABG) surgery will develop post-operative acute kidney injury (AKI). We sought to determine whether biomarkers of kidney tubule dysfunction and injury are associated with long-term risk of acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery. We performed a cohort study using data from the REasons for Geographic And Racial Differences in Stroke (REGARDS), a national, population-based, longitudinal cohort study of 30,239 U.S. adults aged ≥45 years. Of 760 REGARDS participants who underwent CABG surgery after their REGARDS baseline visit, we excluded those with a history of dialysis or kidney transplant, missing laboratory data or with illegible or erroneous records, leaving 394 in the analysis. Exposures included urinary biomarkers of kidney tubule dysfunction (urine alpha-1 microglobulin [A1M], uromodulin [UMOD] and epidermal growth factor [EGF]) and injury (kidney injury molecule-1 [KIM-1]), measured at an average of 5.5 years before CABG surgery. The primary outcome was AKI development following CABG surgery, defined as an increase in serum creatinine ≥0.3 mg/dL from 48 hours prior to CABG surgery to end of hospitalization. Of 394 participants, 176 (45%) experienced post-CABG surgery AKI. Higher baseline urine A1M was associated with higher odds of AKI (adjusted OR 1.34 per 2-fold higher A1M, 95% Confidence Interval (CI): 1.00-1.80). Higher urine UMOD was associated with lower odds of AKI (adjusted OR 0.77 per 2-fold higher UMOD, 95% CI 0.62-0.95). Higher EGF showed a tendency towards lower odds of AKI (adjusted OR 0.79 per 2-fold higher EGF, 95% CI 0.59-1.05). KIM-1 was not associated with AKI (adjusted OR 0.92 per 2-fold higher KIM-1, 95% CI 0.77-1.10). Select biomarkers of kidney tubule dysfunction, but not injury, are associated with future risk of AKI after CABG surgery. Biomarkers measured years before surgery may predict post-CABG surgery AKI.

Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets. Long-term failure of these grafts, however, continues to limit the benefits of surgery. The Cardiothoracic Surgical Trials Network trial of the safety and effectiveness of a Venous External Support (VEST) device is a randomized, multicenter, within-patient trial comparing VEST-supported versus unsupported saphenous vein grafts in patients undergoing CABG. Key inclusion criteria are the need for CABG with a planned internal mammary artery to the left anterior descending and two or more saphenous vein grafts to other coronary arteries. The primary efficacy endpoint of the trial is SVG intimal hyperplasia (plaque + media) area assessed by intravascular ultrasound at 12 months post randomization. Occluded grafts are accounted for in the analysis of the primary endpoint. Secondary confirmatory endpoints are lumen diameter uniformity and graft failure (>50% stenosis) assessed by coronary angiography at 12 months. The safety endpoints are the occurrence of major adverse cardiac and cerebrovascular events and hospitalization within 5 years from randomization. The results of the VEST trial will determine whether the VEST device can safely limit SVG intimal hyperplasia in patients undergoing CABG as treatment for coronary atherosclerotic disease.