Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Biotin-cysteine was used to study protein S-thiolation in isolated rat kidneys subjected to ischemia and reperfusion. After 40 min of ischemia, total protein S-thiolation increased significantly (P < 0.05), by 311%, and remained significantly elevated (P < 0.05), 221% above control, after 5 min of postischemic reperfusion. Treatment of protein samples with 2-mercaptoethanol abolished the S-thiolation signals detected, consistent with the dependence of the signal on the presence of a disulfide bond. With the use of gel filtration chromatography followed by affinity purification with streptavidin-agarose, S-thiolated proteins were purified from CHAPS-soluble kidney homogenate. The proteins were then separated by SDS-PAGE and stained with Coomassie blue. With a combination of matrix-assisted laser desorption ionization time of flight mass spectrometry and LC/MS/MS analysis of protein bands digested with trypsin, a number of S-thiolation substrates were identified. These included the LDL receptor-related protein 2, ATP synthase alpha chain, heat shock protein 90 beta, hydroxyacid oxidase 3, serum albumin precursor, triose phosphate isomerase, and lamin. These represent proteins that may be functionally regulated by S-thiolation and thus could undergo a change in activity or function after renal ischemia and reperfusion.
 ...
PMID:Reversible cysteine-targeted oxidation of proteins during renal oxidative stress. 1287 48

A fundamental aspect of acute renal ischemia is energy depletion, manifest as a falling level of ATP that is associated with a simultaneous rise in AMP. The energy sensor AMP-activated protein kinase (AMPK) is activated by a rising AMP-to-ATP ratio, but its role in acute renal ischemia is unknown. AMPK is activated in the ischemic heart and is reported to phosphorylate both endothelial nitric oxide synthase (eNOS) and acetyl-CoA carboxylase. To study activation of AMPK in acute renal ischemia, the renal pedicle of anesthetized Sprague-Dawley rats was cross-clamped for increasing time intervals. AMPK was strongly activated within 1 min and remained so after 30 min. However, despite the robust activation of AMPK, acute renal ischemia did not increase phosphorylation of the AMPK phosphorylation sites eNOS-Ser(1177) or acetyl-CoA carboxylase-Ser(79). Activation of AMPK in bovine aortic endothelial cells by the ATP-depleting agent antimycin A and the antidiabetic drug phenformin also did not increase phosphorylation of eNOS-Ser(1177), confirming that AMPK activation and phosphorylation of eNOS are dissociated in some situations. Immunoprecipitation studies demonstrated that the dissociation between AMPK activation and phosphorylation of eNOS-Ser(1177) was not due to changes in the physical associations between AMPK, eNOS, or heat shock protein 90. In conclusion, acute renal ischemia rapidly activates the energy sensor AMPK, which is known to maintain ATP reserves during energy stress. The substrates it phosphorylates, however, are different from those in other organs such as the heart.
 ...
PMID:Acute renal ischemia rapidly activates the energy sensor AMPK but does not increase phosphorylation of eNOS-Ser1177. 1591 72

Heat shock proteins (Hsps) are protective in models of transplantation, yet practical strategies to upregulate them remain elusive. The heat shock protein 90-binding agent (HBA) geldanamycin and its analogs (17-AAG and 17-DMAG) are known to upregulate Hsps and confer cellular protection but have not been investigated in a model relevant to transplantation. We examined the ability of HBAs to upregulate Hsp expression and confer protection in renal adenocarcinoma (ACHN) cells in vitro and in a mouse model of kidney ischemia-reperfusion (I/R) injury. Hsp70 gene expression was increased 30-40 times in ACHN cells treated with HBAs, and trimerization and DNA binding of heat shock transcription factor-1 (HSF1) were demonstrated. A three- and twofold increase in Hsp70 and Hsp27 protein expression, respectively, was found in ACHN cells treated with HBAs. HBAs protected ACHN cells from an H2O2-mediated oxidative stress, and HSF1 short interfering RNA was found to abrogate HBA-mediated Hsp induction and protection. In vivo, Hsp70 was upregulated in the kidneys, liver, lungs, and heart of HBA-treated mice. This was associated with a functional and morphological renal protection from I/R injury. Therefore, HBAs mediate upregulation of protective Hsps in mouse kidneys which are associated with reduced I/R injury and may be useful in reducing transplant-associated kidney injury.
 ...
PMID:Heat shock protein 90-binding agents protect renal cells from oxidative stress and reduce kidney ischemia-reperfusion injury. 1856 31