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Bortezomib's Dual Role in Renal Health and Multiple Myeloma Treatment

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— 1 min read

Scientists studying the impact of bortezomib on multiple myeloma, a disease often linked with progressive renal failure, discovered that the therapy has a dual effect on the kidneys. In lab experiments, bortezomib led to a rapid recovery of kidney function in patients with multiple myeloma. However, the researchers also found that bortezomib's impact varies greatly depending on the type of kidney cell it targets, as it activates cell survival genes in human proximal tubular cells but induces apoptosis in glomerular mesangial cells.

Key Takeaways:

  • Bortezomib-based therapy has been reported to lead to a rapid recovery of kidney function in patients with multiple myeloma.
  • In lab experiments, bortezomib led to a 6.37-fold induction of apoptosis and markedly activated caspase-9 and -3 in glomerular mesangial cells but not in proximal tubular epithelial cells.
  • In proximal tubular epithelial cells, bortezomib led to a strong time-dependent degradation of I kappa B-alpha and a long-lasting phosphorylation of both NF-kappa Bp65 and extracellular signal-regulated kinase 1/2.
  • Microarray analysis revealed a time-dependent predominance of antiapoptotic genes compared with proapoptotic genes in bortezomib-treated proximal tubular cells.
  • Bortezomib induced heat shock protein (Hsp) 70 mRNA and protein levels in proximal tubular cells, whereas basal and bortezomib-stimulated Hsp70 protein expression was much weaker in glomerular mesangial cells.
  • The researchers concluded that the concept of bortezomib representing a blocker of both NF-kappa B activation and cell survival should be closely examined, particularly in renal cell types.

Statistics:

  • After 24 hours of stimulation, 50 nM bortezomib led to a 6.37-fold induction of apoptosis in glomerular mesangial cells.
  • Microarray analysis revealed a time-dependent predominance of antiapoptotic genes (63.2%) compared with proapoptotic genes (36.8%) in bortezomib-treated proximal tubular cells.
  • Bortezomib induced Bcl-2-associated athanogene (BAG) 3 mRNA and protein expression, but inhibited BAG5 mRNA levels in proximal tubular cells.

Sources:

  • R. Sarkozi, H. Schramek, Innsbruck Medical University, et al. "Bortezomib-Induced Survival Signals and Genes in Human Proximal Tubular Cells." Journal of Pharmacology and Experimental Therapeutics, vol. 327, no. 3, 2008, pp. 645-656.
  • American Society Pharmacology Experimental Therapeutics, 9650 Rockville Pike, Bethesda, MD 20814-3995, USA.

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