Insulin-regulated aminopeptidase in adipocyte is Cys-specific and affected by obesity

Author(s)

Alponti, Rafaela Fadoni ^{[1, 2, 3]} ; Viana, Luciana Godoy ^{[1, 3]} ; Yamanouye, Norma ^{[1, 3]} ; Silveira, Paulo Flavio ^{[1, 3]}

Affiliation

^[1] Inst Butantan, Pharmacol Lab, BR-05503900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Dept Physiol, Sao Paulo - Brazil

^[3] Inst Butantan, Unit Translat Endocrine Physiol & Pharmacol, BR-05503900 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF MOLECULAR ENDOCRINOLOGY; v. 55, n. 1, p. 1-8, AUG 2015.
• Web of Science Citations: 3

Abstract

Insulin-regulated aminopeptidase (IRAP, EC 3.4.11.3) in adipocytes is well known to traffic between high (HDM) and low (LDM) density microsomal fractions toward the plasma membrane (MF) under stimulation by insulin. However, its catalytic preference for aminoacyl substrates with N-terminal Leu or Cys is controversial. Furthermore, possible changes in its traffic under metabolic challenges are unknown. The present study investigated the catalytic activity attributable to EC 3.4.11.3 in HDM, LDM and MF from isolated adipocytes of healthy (C), food deprived (FD) and monosodium glutamate (MSG) obese rats on aminoacyl substrates with N-terminal Cys or Leu, in absence or presence of insulin. Efficacy and reproducibility of subcellular adipocyte fractionation procedure were demonstrated. Comparison among HDM vs LDM vs MF intragroup revealed that hydrolytic activity trafficking from LDM to MF under influence of insulin in C, MSG and FD is only on N-terminal Cys. In MSG the same pattern of anterograde traffic and aminoacyl preference occurred independently of insulin stimulation. The pathophysiological significance of IRAP in adipocytes seems to be linked to comprehensive energy metabolism related roles of endogenous substrates with N-terminal cysteine pair such as vasopressin and oxytocin. (AU)

• FAPESP's process: 10/01385-5 - Aminopeptidases, prolil oligopeptidase and representative peptides in adipocytes from obese and food deprived rats
• Grantee: Paulo Flávio Silveira
• Support Opportunities: Regular Research Grants