Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms

Si, Jin; Ge, Yan; Zhuang, Shougang; Juan Wang, Li; Chen, Shan; Gong, Rujun
April 2013
Kidney International;Apr2013, Vol. 83 Issue 4, p635
Academic Journal
Adrenocorticotropic hormone (ACTH) has a renoprotective effect in chronic kidney disease; however, its effect on acute kidney injury (AKI) remains unknown. In a rat model of tumor necrosis factor (TNF)-induced AKI, we found that ACTH gel prevented kidney injury, corrected acute renal dysfunction, and improved survival. Morphologically, ACTH gel ameliorated TNF-induced acute tubular necrosis, associated with a reduction in tubular apoptosis. While the steroidogenic response to ACTH gel plateaued, the kidney-protective effect continued to increase at even higher doses, suggesting steroid-independent mechanisms. Of note, ACTH also acts as a key agonist of the melanocortin system, with its cognate melanocortin 1 receptor (MC1R) abundantly expressed in renal tubules. In TNF-injured tubular epithelial cells in vitro, ACTH reinstated cellular viability and eliminated apoptosis. This beneficial effect was blunted in MC1R-silenced cells, suggesting that this receptor mediates the anti-apoptotic signaling of ACTH. Moreover, ACTH gel protected mice against cecal ligation puncture-induced septic AKI better than α-melanocyte-stimulating hormone: a protein equal in biological activity to ACTH except for steroidogenesis. Thus, ACTH has additive renoprotective actions achieved by both steroid-dependent mechanisms and MC1R-directed anti-apoptosis. ACTH may represent a novel therapeutic strategy to prevent or treat AKI.


Related Articles

  • Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death. Tsuruya, Kazuhiko; Ninomiya, Toshiharu; Tokumoto, Masanori; Hirakawa, Makoto; Masutani, Kohsuke; Taniguchi, Masatomo; Fukuda, Kyoichi; Kanai, Hidetoshi; Kishihara, Kenji; Hirakata, Hideki; Iida, Mitsuo // Kidney International;Jan2003, Vol. 63 Issue 1, p72 

    Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death. Background. Tumor necrosis factor (TNF) receptor family members, such as Fas and TNF receptor 1 (TNFR1), are thought to induce apoptosis in a variety of cells and organs. Although a...

  • Effects of Melanocortin 1 Receptor Agonists in Experimental Nephropathies. Lindskog Jonsson, Annika; Granqvist, Anna; Elvin, Johannes; Johansson, Martin E.; Haraldsson, Börje; Nyström, Jenny // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    Nephrotic syndrome, characterized by massive proteinuria, is caused by a large group of diseases including membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS). Although the underlying mechanisms are beginning to unravel, therapy is unspecific and far from efficient. It has...

  • Effects of AgRP Inhibition on Energy Balance and Metabolism in Rodent Models. Dutia, Roxanne; Kim, Andrea J.; Modes, Matthew; Rothlein, Robert; Shen, Jane M.; Tian, Ye Edward; Ihbais, Jumana; Victory, Sam F.; Valcarce, Carmen; Wardlaw, Sharon L. // PLoS ONE;Jun2013, Vol. 8 Issue 6, p1 

    Activation of brain melanocortin-4 receptors (MC4-R) by α-melanocyte-stimulating hormone (MSH) or inhibition by agouti-related protein (AgRP) regulates food intake and energy expenditure and can modulate neuroendocrine responses to changes in energy balance. To examine the effects of AgRP...

  • Apoptotic pathways in ischemic acute renal failure. Kaushal, Gur P.; Basnakian, Alexi G. // Kidney International;Aug2004, Vol. 66 Issue 2, p500 

    Apoptotic pathways in ischemic acute renal failure. The study of cell death has emerged as an important and exciting area of research in cell biology. Although two kinds of cell death, apoptosis and necrosis, are recognized, one of the major advances in our understanding of cell death has been...

  • Multiple sclerosis, relapses, and the mechanism of action of adrenocorticotropic hormone. Perrin Ross, Amy; Ben-Zacharia, Aliza; Harris, Colleen; Smrtka, Jennifer // Frontiers in Neurology;Mar2013, Vol. 4, p1 

    Relapses in multiple sclerosis (MS) are disruptive and frequently disabling for patients, and their treatment is often a challenge to clinicians. Despite progress in the understanding of the pathophysiology of MS and development of new treatments for long-term management of MS, options for...

  • EPO and α-MSH prevent ischemia/reperfusion-induced down-regulation of AQPs and sodium transporters in rat kidney. Hong Gong; Weidong Wang; Taw-Hwan Kwon; Jonassen, Thomas; Chunling Li; Ring, Troels; Frøkiær, Jørgen; Nielsen, Søren // Kidney International;Aug2004, Vol. 66 Issue 2, p683 

    EPO and α-MSH prevent ischemia/reperfusion-induced down-regulation of AQPs and sodium transporters in rat kidney. Background. Ischemia-induced acute renal failure (ARF) is known to be associated with significant impairment of urinary concentrating ability and down-regulation of renal...

  • Adrenocorticotropic Hormone (ACTH) But Not Alpha-Melanocyte Stimulating Hormone (alpha-MSH) as a... Rose, Jack // Journal of Investigative Dermatology;Apr98, Vol. 110 Issue 4, p456 

    Investigates the role of adrenocorticotropic hormone (ACTH) and alpha-melanocyte stimulating hormone as mediators of adrenalectomy induced hair growth in mink. Period when winter hair growth usually begins; Possible influence of ACTH on the metabolism of steroid hormones in the skin;...

  • Retarding the progression of renal disease. Brenner, Barry M. // Kidney International;Jul2003, Vol. 64 Issue 1, p370 

    Presents a case of a woman with acute renal failure. Case history of the patient; Understanding of the mechanisms of progressive nephron loss; Evaluation of amenorrhea.

  • Post-ischemic acute renal failure protects proximal tubules from O2 deprivation injury, possibly by inducing uremia. Zager, Richard A.; Iwata, Mineo; Burkhart, Kristin M.; Schimpf, Brian A. // Kidney International;Jun1994, Vol. 45 Issue 6, p1760 

    Rats within the early maintenance phase of post-ischemic acute renal failure (ARF) can resist additional ischemic insults. This study assessed whether this protection exists directly at the tubular cell level, and if so, whether it is a consequence of prior cell injury (for example, due to...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics