[Spinocerebellar ataxia 2 develop lower motor neuron involvement as an initial symptom: a case report].

A 36-year-old man has developed weakness of left thumb and atrophy of left thenar muscle and left first dorsal interosseous muscle without sensory disturbance for a year. A nerve conduction study revealed decreases in the amplitude of compound muscle action potentials and occurrence of F-waves on left medial nerve. Needle electromyography examination revealed positive sharp waves and later recruited motor units on left abductor pollicis brevis muscle. Brain MRI showed atrophy of bilateral cerebellar hemisphere. His grandmother and his two uncles have been diagnosed as spinocerebellar degeneration. After discharge, he developed bilateral lower limb ataxia. Genetic analysis showed heterozygous CAG repeat expansion (19/39) in ATXN2 gene, being diagnosed as spinocerebellar ataxia 2 (SCA2). A previous report has shown that motor neuron involvement is recognized as part of SCA2 in the same pedigree with full CAG repeat expansions in ATXN2 gene. We here report the patient with lower motor neuron involvement as an initial symptom of SCA2.

Endoplasmic reticulum stress induced by tunicamycin increases resistin messenger ribonucleic acid through the pancreatic endoplasmic reticulum eukaryotic initiation factor 2α kinase-activating transcription factor 4-CAAT/enhancer binding protein-α homologous protein pathway in THP-1 human monocytes.

AIMS/INTRODUCTION: Resistin, secreted from adipocytes, causes insulin resistance in mice. In humans, the resistin gene is mainly expressed in monocytes and macrophages. Tunicamycin is known to induce endoplasmic reticulum (ER) stress, and reduce resistin gene expression in 3T3-L1 mouse adipocytes. The aim of the present study was to examine whether ER stress affects resistin gene expression in human monocytes. MATERIALS AND METHODS: The relationship between resistin messenger ribonucleic acid (mRNA) and ER stress markers mRNA was analyzed by reverse transcription polymerase chain reaction in isolated monocytes of 30 healthy volunteers. The effect of endotoxin/lipopolysaccharides or tunicamycin on resistin gene expression was analyzed in THP-1 human monocytes. Signaling pathways leading to resistin mRNA were assessed by the knockdown using small interfering RNA or overexpression of key molecules involved in unfolded protein response. RESULTS: Resistin mRNA was positively associated with immunoglobulin heavy chain-binding protein (BiP) or CAAT/enhancer binding protein-α homologous protein (CHOP) mRNA in human isolated monocytes. In THP-1 cells, lipopolysaccharides increased mRNA of BiP, pancreatic endoplasmic reticulum eukaryotic initiation factor 2α kinase (PERK) and CHOP, as well as resistin. Tunicamycin also increased resistin mRNA. This induction appeared to be dose- and time-dependent. Tunicamycin-induced resistin mRNA was inhibited by chemical chaperone, 4-phenylbutyric acid. The knockdown of either PERK, activating transcription factor 4 (ATF4) or CHOP reduced tunicamycin-induced resistin mRNA. Conversely, overexpression of ATF4 or CHOP increased resistin mRNA. CONCLUSIONS: Endoplasmic reticulum stress induced by tunicamycin increased resistin mRNA through the PERK-ATF4-CHOP pathway in THP-1 human monocytes. ER stress could lead to insulin resistance through enhanced resistin gene expression in human monocytes.