Overexpression of myosin-IIB in the brain of a rat model of streptozotocin-induced diabetes

Abstract

The Ca(2+)/calmodulin complex interacts with and regulates various enzymes and target proteins known as calmodulin-binding proteins (CaMBPs). This group of proteins includes molecular motors such as myosins. In this study, we show that non-muscle myosin-IIB is overexpressed in the brains of diabetic rats. We isolated CaMBPs from the brains of non-diabetic rats and rats with streptozotocin-induced diabetes and purified them by immobilized-calmodulin affinity chromatography. The proteins were eluted with EGTA and urea, separated by SDS-PAGE, digested and submitted to peptide mass fingerprinting analysis. Thirteen intense bands were found in both types of brains, two were found exclusively in non-diabetic brains and four were found exclusively in diabetic brains. A large fraction of the eluted proteins contained putative IQ motifs or calmodulin-binding sites. The results of the myosin-IIB affinity chromatography elution, western blot and RT-PCR analyses suggest that myosin-IIB protein and mRNA are expressed at high levels in diabetic brains. This is the first study that has demonstrated differential expression of CaMBPs in diabetic and non-diabetic brain tissue through a comparative proteomic analysis, and it opens up a new approach to studying the relationship between the expression of myosins in the brain, hyperglycemia and intracellular calcium regulation.

Myosins Are Differentially Expressed under Oxidative Stress in Chronic Streptozotocin-Induced Diabetic Rat Brains

“…Myosin-IIB modulates neurotransmitter release from synapses [83] while myosin-Va mediates synaptic vesicle trafficking [84]. We recently demonstrated that acute diabetes (20 days) alters protein and mRNA expression of myosin-IIB and myosin-Va in the rat brains [21, 23]. In the present study, we revealed an increased protein and mRNA expression of myosin-IIB and a decreased one of myosin-Va in chronic diabetic rat brains (90 days).…”

“…In the present study, we revealed an increased protein and mRNA expression of myosin-IIB and a decreased one of myosin-Va in chronic diabetic rat brains (90 days). It is possible that these translational and transcriptional changes are due to low insulin level and high glucose level in circulation providing a possible dysfunction in vesicle/organelle movement [21, 23]. …”

“…In spite of the recent studies that have shown relationship between diabetes and the expression of molecular motors, as myosin-IIB [21], myosin heavy-chain [29], myosin-Va [23, 25], and myosin-IXB [30], the pathways linked among myosin expression, oxidative stress, and diabetes mellitus are still unclear. The present study aimed to evaluate the effect of the use of antioxidant supplementation on myosins expression in brain of chronic streptozotocin-induced diabetes experimental rat model.…”

Myosin Va but Not nNOSα is Significantly Reduced in Jejunal Musculomotor Nerve Terminals in Diabetes Mellitus

“…One intriguing question that posits from these observations is that if myosin Va is an important regulator of both vesicular and non-vesicular neurotransmission in both the central and peripheral nervous system, how can neuronal physiological function continue to operate, albeit at a lower level of performance, despite reduction, or absence of myosin Va. One likely reason of how neurotransmission function is sustained in the face of diminished myosin Va may be due to neuroplastic changes. For example, it has been reported that in the brain, similar diabetic conditions that result in myosin Va reduction also results in increased expression of non-muscle myosin II (NMMII) ( 64 ). NMMII plays a critical role in vesicular neurotransmitter release at the cortex of the nerve terminal.…”

Aspectos Morfológicos Dos Sistemas Corporais

“…CALÁBRIA et al, 2011;DA COSTA et al, 2013). Os ratos não diabéticos receberam injeção do mesmo volume de tampão citrato, nas mesmas condições dos diabéticos induzidos.…”