Histone H4 stimulates glucose transport activity in rat skeletal muscle

Abstract

We investigated the effects of purified histone H4 on glucose transport activity in rat soleus and flexor digitorum brevis muscles. Histone H4, at concentrations up to 11.8 microM, increased 2-deoxyglucose (2-DG) uptake in a dose-dependent fashion. However, at concentrations higher than 11.8 microM, H4 caused a decrease in 2-DG uptake from the maximum, suggesting a secondary inhibitory action of this compound. The maximal effect of H4 on 2-DG uptake was not additive to the maximal effect of insulin. Moreover, 2-DG uptake in the presence of both H4 and insulin was significantly lower than the 2-DG uptake in the presence of insulin alone. The maximal effect of H4 on stimulation of 2-DG uptake was neither additive nor inhibitory to the maximal effects of the intracellularly acting insulin mimetics sodium vanadate or H2O2. It was, on the other hand, additive to the maximal effects of muscle contractions. Also, in contrast with the effects of H4 on insulin-stimulated 2-DG uptake, H4 did not inhibit insulin-like growth factor-I (IGF-I)-stimulated 2-DG uptake, as the maximal effects of H4 and IGF-I were additive. Scatchard analysis of the binding of 125I-insulin in the absence or presence of histone H4 revealed that H4 increased the specific binding of insulin without affecting receptor affinity. These data suggest that H4 interacts with the insulin, rather than the hypoxia/contraction, pathway for activation of glucose transport in muscle tissue, and that H4 acts either directly or indirectly to increase the number of insulin receptors at the surface of the muscle cell. This interaction does not appear to occur with the similar, although distinct, IGF-I receptor. These studies may provide additional insight into the complex signal-transduction systems of insulin action.

Histones and basic polypeptides activate Ca2+/cation influx in various cell types

“…The surface expression of these proteins was often found associated with cell activation [25,26,28,30], or is relevant to egg fertilization [29], which involves cell ionic events. H2A and H2B have a primary structure identical with those of the homoeostatic thymus hormones HTH a and HTH b respectively [22,23], and the ovarian gonadotropin-releasing hormone-binding inhibitor was identified as H2A [54].…”

“…Previous studies suggested a hormone-like activity for some histones ( [22] ; see [23] for additional references), and hypothesized additional functions for histones apart from being nucleosoma components [24]. Histones, or proteins resembling them, have been shown to be present on the surface of various cell types [25][26][27][28][29][30].…”

“…Histones, or proteins resembling them, have been shown to be present on the surface of various cell types [25][26][27][28][29][30]. Moreover, interactions between extracellular basic proteins\polypeptides and PM surface (negatively charged) components may also take place under a variety of circumstances eventually involving signalling events ( [31][32][33][34] ; see [23] for additional references). We have therefore investigated in detail the effects of histone H2A (H2A) and various other basic proteins\polypeptides on PM Ca# + \cation fluxes in several cell types in suspension, namely ETCs, Jurkat T-lymphocytes, rat thymocytes and hepatocytes, Friend erythroleukaemia and PC12 rat pheochromocytoma cells.…”