K ATP Channel Gene Expression Is Induced by Urocortin and Mediates Its Cardioprotective Effect
Authors: D S Latchman
P A Townsend
R Ferrari
M Hubank
A Tinker
T Scarabelli
K M Lawrence
R A Knight
A Chanalaris
A Stephanou
L Comini
E Pasini
Journal: Circulation (2002)
Discipline: CLINICAL MEDICINE
Keywords: Urocortin; cardioprotective agent; gene expression; Kir 6.1; cardiac potassium channel subunit
Affiliations: Medical Molecular Biology Unit, Institute of Child Health, University College London, London, England.

Abstract:  Background: Urocortin is a novel cardioprotective agent that can protect cardiac myocytes from the damaging effects of ischemia/reperfusion both in culture and in the intact heart and is effective when given at reperfusion. Methods and results: We have analyzed global changes in gene expression in cardiac myocytes after urocortin treatment using gene chip technology. We report that urocortin specifically induces enhanced expression of the Kir 6.1 cardiac potassium channel subunit. On the basis of this finding, we showed that the cardioprotective effect of urocortin both in isolated cardiac cells and in the intact heart is specifically blocked by both generalized and mitochondrial-specific K(ATP) channel blockers, whereas the cardioprotective effect of cardiotrophin-1 is unaffected. Conversely, inhibiting the Kir 6.1 channel subunit greatly enhances cardiac cell death after ischemia. Conclusions: This is, to our knowledge, the first report of the altered expression of a K(ATP) channel subunit induced by a cardioprotective agent and demonstrates that K(ATP) channel opening is essential for the effect of this novel cardioprotective agent. 

Retracted: No

PubPeer comments:
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 #5 The correction is condoning image flipping. , 
  **Figure 6**. Effects of 5-HD, glibenclamide (Gbc), and Ucn on DP and EDP during I R (30 minutes of global ischemia followed by 60 minutes of reperfusion) in the isolated rat heart. DP and EDP in control heart exposed to I R are shown in panel a; changes in DP and EDP induced by 5-HD (0.5 mmol L) and glibenclamide (0.05 mmol L) given during the aerobic phase before I R, and Ucn given before ischemia and during reperfusion are reported in panels b, c, and d, respectively. Hemodynamic effects of Ucn given before and after ischemia in isolated hearts pretreated with 5-HD and glibenclamide are shown in panels e and f, respectively.  **Figure 7**. Effect of cycloheximide (1.0 mg kg) on the hemodynamic effects of Ucn in the intact heart. a, Control I R. b, Pretreatment with cycloheximide (Chx) for 3 hours before heart isolation. c, Infusion of Ucn, pre- and postischemia. d, Pretreatment with cycloheximide before heart isolation and infusion of Ucn, pre- and postischemia. 6(a), (b), (d), (e) = 7(a) - (d). ![file] Assuming this to be a mistake, I am concerned that no-one has mentioned this in the 16 years since publication, and that the authors missed the chance to correct it at the same time as they replaced Fig 3(a). , 
 At left: Figure 7. Upper right:  **Figure 1**. Effects of urocortin (Ucn) on developed pressure (DP) and diastolic pressure (dP) during ischemia reperfusion (I R) in the isolated rat heart. Developed pressure and dP in control heart exposed to I R are shown in a; changes in DP and dP induced by Ucn given before I, before and after R, and over R alone are reported in b, c and d, respectively . From [Scarabelli et al. (2002)] . Lower right: 1(A) and 7(A) superimposed; 1(C) and 7(C) superimposed. ![file] These are supposed to be different data sets. , 
 #8 The similar graphs of Figure 7A (this paper) and 1A of Scarabelli et al. (2002) depict a control condition... heart non-recovery from ischaemia reperfusion in the absence of any treatment. It occurred to me that the authors had reused the same data in both papers, accounting for the similarity. But this explanation does not hold for the data points at -30 are not identical. The resemblance remains a mystery. Out of curiosity I included the control-condition results plotted as Figure 5A of [Townsend et al. (2004)] and as 1C of [Scarabelli et al. (2004)] . The separate plots are lined up at the left. In the middle, 7A and 1A superimposed. ![file] At the right, I overlaid 5A on the 7A 1A combination. The dP function shows some recognisable differences but the sP function is a remarkably good match. Below that, Figure 1C overlaid on the 7A 1A combination. This time the dP function shows an impressively good replication (especially considering the error bars) although the sP function deviates at some time-points. , 
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 The top secret UCL report on the Masteru2019s laboratory gone rogue was recently leaked to the Telegraph **Leading university embroiled in major research scandal** https: www.telegraph.co.uk education 2018 05 16 one-britains-leading-universities-embroiled-majorresearch-scandal *u201cbut in seven others, it concluded there was evidence of fraud.u201d* In keeping with the secrecy, this article has been stealth corrected. We will probably never find out whether the three wise men considered it to be one of the seven fraudies or not. ![image] , 
 https: www.buzzfeednews.com article peteraldhous david-latchman-scientific-misconduct https: www.theguardian.com science 2019 jul 01 research-misconduct-claim-upheld-against-former-head-of-ucl-lab ,