TAT-HSP27 Peptide Improves Neurologic Deficits via Reducing Apoptosis After Experimental Subarachnoid Hemorrhage

Abstract

Cell apoptosis plays an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH). Heat shock protein 27 (HSP27), a member of the small heat shock protein (HSP) family, is induced by various stress factors and exerts protective role on cells. However, the role of HSP27 in brain injury after SAH needs to be further clarified. Here, we reported that HSP27 level of cerebrospinal fluid (CSF) is increased obviously at day 1 in patients with aneurysmal SAH (aSAH) and related to the grades of Hunt and Hess (HH), World Federation of Neurological Surgeons (WFNS), and Fisher score. In rat SAH model, HSP27 of CSF is first increased and then obviously declined; overexpression of HSP27, not knockdown of HSP27, attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex; and overexpression of HSP27 effectively suppresses SAH-elevated activation of mitogen-activated protein Kinase Kinase 4 (MKK4), the c-Jun N-terminal kinase (JNK), c-Jun, and caspase-3. In an in vitro hemolysate-damaged cortical neuron model, HSP2765−90 peptide effectively inhibits hemolysate-induced neuron death. Furthermore, TAT-HSP2765−90 peptide, a fusion peptide consisting of trans-activating regulatory protein (TAT) of HIV and HSP2765−90 peptide, effectively attenuates SAH-induced neurological deficit and cell apoptosis in the basal cortex of rats. Altogether, our results suggest that TAT-HSP27 peptide improves neurologic deficits via reducing apoptosis.

RETRACTED: Ravoxertinib Improves Long-Term Neurologic Deficits after Experimental Subarachnoid Hemorrhage through Early Inhibition of Erk1/2

“…injection, which was performed as previously described. 35 In brief, rats following SAH were treated with a single i.c.v. injection (0.8 mm posterior, 1.2 mm lateral, and 3.8 mm depth) of RAH (5 μL, 50 μM; HY-15947A, MedChemExpress) or vehicle (5 μL, saline) with a 10 μL Hamilton syringe on a stereotaxic apparatus.…”

“…In this study, RAH was administered by an intracerebroventricular (i.c.v.) injection, which was performed as previously described . In brief, rats following SAH were treated with a single i.c.v.…”

Functional Diversity of Mammalian Small Heat Shock Proteins: A Review

“…Similarly, TAT-HSPB8 was also proven to inhibit oxidative stress-induced apoptosis in hippocampal neuronal cells [49]. Furthermore, TAT-HSPB1 65-90 peptide attenuates neurological deficits and cortical apoptosis after experimental subarachnoid hemorrhage (SAH) [216]. Surprisingly, a study showed that the TAT-HSPB1 12-35 peptide induces lysosomal membrane permeabilization and the release of cathepsin D from lysosomes after entering clear cell renal cell carcinoma cells, resulting in apoptosis and inhibition of proliferation, which indicates that TAT-HSPB1 12-35 is a potential therapeutic agent for renal cancer [217].…”

The role of heat shock proteins in the pathogenesis of heart failure (Review)

“…The intracellular function of the HSP27 chaperone is regulated by phosphorylation and dephosphorylation in large aggregates that modulate the assembly of an ATP-independent network. As a chaperone, HSP27 is involved in DNA stabilization, supports antioxidant responses and also acts as an anti-apoptotic factor (92)(93)(94). Extracellular release of HSP27 from tissues where blood vessels are affected by atherosclerosis may result from cellular injury or occur in association with secretory lysosomes or exosomes.…”